Muramyl peptide derivatives and immunoregulating compositions containing them

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to novel muramyl peptide derivatives. The muramyl peptide derivatives of the present invention acts on in vivo immunomechanism of human beings and livestock (in particular cells relevant to immune responses) and are useful as immunoregulating agents.
2. Description of the Prior Art
Muramyl peptides are known to possess various biological activities. That is,1they possess in vitro activities such as;
(1) the action on cells related to immune responses (for example, monocytes or macrophages, B cells, T cells, natural killer (NK) cells and the like),
(2) the action on cells other than those mentioned above (for example, platelets, endothelial cells, fibroblasts and the like), and
(3) the action which activates complement systems.
Further they show in vivo activities such as (1) immunoregulating action, and (2) enhancement of natural resistance [see Saishin Igaku, 43, No. 6, pp. 1268-1276 (1988) in Japan].
Known muramyl peptide derivatives are, for example, B30-muramyl dipeptide [Kusumoto et al; Tetrahedron letters, 49 pp. 4899-4902(1978)], muramyl dipetide-lysine [Matsumoto et al, Immunostimulants, pp. 79-97 (1987)]and those discribed in Japanese Published Unexamined Patent Application Nos. 172399/1983, 20297/1984 and 275299/1986.
However, it is still desired to develop compounds other than the known muramyl dipeptide derivatives which have more excellent activity and less toxicity.
SUMMARY OF THE INVENTION
According to the present invention, a muramyl dipeptide derivative is provided, which is represented with the following formula (I): ##STR6## wherein "Ala" is ##STR7## "isoGln" is R.sub.1 is R.sub.3 O- or R.sub.3 S- ##STR8## k is an integer from 8 to 12; q is an integer from 10 to 22) or R.sub.3 is ##STR9## (m is an integer from 11 to 17; n is an integer from 11 to 17)]; and R.sub.2 is a hydrogen atom or--CO--(CH.sub.2).sub.p --CH.sub.3 (p is an integer from 8 to 22).
The present invention also provides an immunoregulating composition comprising a compound of the formula (I) and a pharmaceutically acceptable carrier.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the formula (I), examples of the groups R.sub.3 in the group -OR.sub.3 or -SR.sub.3 include 3-dodecanoyloxydodecanoyl, 3-tridecanoyloxydodecanoyl, 3-tetradecanoyloxydodecanoyl, 3-pentadecanoyloxydodecanoyl, 3-hexadecanoyloxydodecanoyl, 3-heptadecanoyloxydodecanoyl, 3-octadecanoyloxydodecanoyl, 3-nonadecanoyloxydodecanoyl, 3-eicosanoyloxydodecanoyl, 3-docosanoyloxydodecanoyl, 3-heneicosanoyloxydodecanoyl, 3-tricosanoyloxydodecanoyl, 3-tetracosanoyloxydodecanoyl, 3-dodecanoyloxytridecanoyl, 3-tridecanoyloxytridecanoyl, 3-tetradecanoyloxytridecanoyl, 3-pentadecanoyloxytridecanoyl, 3-hexadecanoyloxytridecanoyl, 3-heptadecanoyloxytridecanoyl, 3-octadecanoyloxytridecanoyl, 3-nonadecanoyloxytridecanoyl, 3-eicosanoyloxytridecanoyl, 3-docosanoyloxytridecanoyl, 3-heneicosanoyloxytridecanoyl, 3-tricosanoyloxytridecanoyl, 3-tetracosanoyloxytridecanoyl, 3-dodecanoyloxytetradecanoyl, 3-tridecanoyloxytetradecanoyl, 3-tetradecanoyloxytetradecanoyl, 3-pentadecanoyloxytetradecanoyl, 3-hexadecanoyloxytetradecanoyl, 3-heptadecanoyloxytetradecanoyl, 3-octadecanoyloxytetradecanoyl, 3-nonadecanoyloxytetradecanoyl, 3-eicosanoyloxytetradecanoyl, 3-docosanoyloxytetradecanoyl, 3-heneicosanoyloxytetradecanoyl, 3-tricosanoyloxytetradecanoyl, 3-tetracosanoyloxytetradecanoyl, 3-dodecanoyloxypentadecanoyl, 3-tridecanoyloxypentadecanoyl, 3-tetradecanoyloxypentadecanoyl, 3-pentadecanoyloxypentadecanoyl, 3-hexadecanoyloxypentadecanoyl, 3-heptadecanoyloxypentadedanoyl, 3-octadecanoyloxypentadecanoyl, 3-nonadecanoyloxypentadecanoyl, 3-eicosanoyloxypentadecanoyl, 3-docosanoyloxypentadecanoyl, 3-heneicosanoyloxypentadecanoyl, 3-tricosnoyloxypentadecanoyl, 3-tetracosanoyloxypentadecanoyl, 3-dodecanoyloxyhexadecanoyl, 3-tridecanoyloxyhexadecanoyl, 3-tetradecanoyloxyhexadecanoyl, 3-pentadecanoyloxyhexadecanoyl, 3-hexadecanoyloxyhexadecanoyl, 3-heptadecanoyloxyhexadecanoyl, 3-octadecanoyloxyhexadecanoyl, 3-nonadecanoyloxyhexadecanoyl, 3-eicosanoyloxyhexadecanoyl, 3-docosanoyloxyhexadecanoyl, 3-heneicosanoyloxyhexadecanoyl, 3-tricosanoyloxyhexadecanoyl, 3-tetracosanoyloxyhexadecanoyl, 2-dodecyltetradecanoyl, 2-tridecyltetradecanoyl, 2-tetradecyltetradecanoyl, 2-pentadecyltetradecanoyl, 2-hexadecyltetradecanoyl, 2-heptadecyltetradecanoyl, 2-octadecyltetradecanoyl, 2-tetradecylpentadecanoyl, 2-pentadecylpentadecanoyl, 2-hexadecylpentadecanoyl, 2-heptadecylpentadecanoyl, 2-octadecylpentadecanoyl, 2-dodecylhexadecanoyl, 2-tridecylhexadecanoyl, 2-tetradecylhexadecanoyl, 2-pentadecylhexadecanoyl, 2-hexadecylhexadecanoyl, 2-heptadecylhexadecanoyl, 2-octadecylhexadecanoyl, 2-dodecylpentadecanoyl, 2-tridecylpentadecanoyl, 2-tetradecylpentadecanoyl, 2-pentadecylpentadecanoyl, 2-hexadecylpentadecanoyl, 2-heptadecylpentadecanoyl, 2-octadecylpentadecanoyl, 2-dodecylhexadecanoyl, 2-tridecylhexadecanoyl, 2-tetradecylhexadecanoyl, 2-pentadecylhexadecanoyl, 2-hexadecylhexadecanoyl, 2-heptadecylhexadecanoyl, 2-octadecylhexadecanoyl, 2-dodecylheptadecanoyl, 2-tridecylheptadecanoyl, 2-tetradecylheptadecanoyl, 2-pentadecylheptadecanoyl, 2-hexadecylheptadecanoyl, 2-octadecylheptadecanoyl, 2-dodecylocta- decanoyl, 2-tridecyloctadecanoyol, 2-tetradecylocta- decanoyl, 2-pentadecyloctadecanoyl, 2-hexadecylocta- decanoyl, 2-heptadecyloctadecanoyl, 2-octadecylocta- decanoyl, 2-dodecylnonadecanoyl, 2-tridecylnona- decanoyl, 2-tetradecylnonadecanoyl, 2-pentadecylnona- decanoyl, 2-hexadecylnonadecanoyl, 2-heptadecylnona- decanoyl, 2-octadecylnonadecanoyl, 2-dodecyleicosanoyl, 2-tridecyleicosanoyl, 2-tetradecyleicosanoyl, 2-pentadecyleicosanoyl, 2-hexadecyleicosanoyl, 2-heptadecyleicosanoyl and 2-octadecyleicosanoyl groups.
Preferred groups of R3 are 3-tetradecanoyloxytetradecanoyl, 3-hexadecanoyloxytetradecanoyl, 3-octadecanoyloxytetradecanoyl, 3-tetracosanoyloxytetradecanoyl and 2-tetradecylhexadecanoyl groups.
Examples of R.sub.2 include hydrogen atom, decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, eicosanoyl, docosanoyl, heneicosanoyl, tricosanoyl and tetracosanoyl groups.
R.sub.2 is preferably hydrogen atom or tetradecanoyl group.
Preferably, "Ala" is an L-alanine residue, and "isoGln" is a residue derivated from D-isoglutamine.
The compounds of the formula (I) of the present invention are basically muramyl dipeptide derivatives, in which the muramyl dipeptide moiety has preferably the same steric configuration as that of the muramyl dipeptide moiety in natural muramyl dipeptides. Namely, the moieties of muraminic acid and dipeptide in the present muramyl dipeptides have D-steric configuration and L-alanine-D-isoglutamine configuration, respectively. However, the muramyl dipeptides of the present invention may be those having other possible steric configurations.
The group --OR.sub.3 or --SR.sub.3 in the definition of the formula (I) preferably combines with the saccharide moiety in the form of .alpha.-bond and .beta.-bond, respectively.
The acyloxyacyl group in R.sub.3 has an asymmetric carbon atom and may be in the form of D- or L-isomer, or racemic mixture.
Interesting compounds belonging to the formula (I) in the present invention include:
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-tetradecylhexadecanoyl)-60 -D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-(2-tetradecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-0-[2-tetradecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-(2-tetradecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-tetradecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-(2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-(2-tetradecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-1-S-(2-tetradecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-(2-tetradecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-{(3R)-3-tetradecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-tetradecanolyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-0-((3R)-3-tetradecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-tetradecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-([3R)-3-tetradecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-tetradecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-S-([3R)-3-tetradecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R)-3-tetradecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-hexadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-hexadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-hexadecanoyloxytetradecanoyl-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-hexadecanoyloxytetradecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-hexadecanoyloxytetradecanoyl)-1-thio-8-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-hexadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-hexadecanoyloxytetradecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-{(3R)-3-hexadecanoyloxytetradecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-octadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-hexadecanoyloxytetradecanoyl}-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-octadecanoyloxytetradecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-octadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-octadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-octadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-octadecanoyloxytetradecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl1-S-((3R)-3-octadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-tetracosanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-tetracosanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-({3R)-3-tetracosanoyloxytetradecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-tetracosanoyloxytetradecanoyl}-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-tetracosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-tetracosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-tetracosanoyloxytetradecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R)-3-tetracosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-(2-tetradecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-d-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-(2-tetradecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-(2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-(2-tetradecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methyester
N-[2-0-(2-Acetamido-2,3-dideoxy-6-0-hyxadecanoyl-1-S-(2-tetradecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methyester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-dodecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-dodecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxytetradecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxytetradecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxytetradecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-dodecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-dodecanoyloxytetradecanoyl)-1-thio-8-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxytetradecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxytetradecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(3R)-3-dodecanoyloxytetradecanoyl-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-dodecanoyl-1-0-((3R)-3-tetradecanoyloxytetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-((3R)-3-tetradecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-tetradecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-((3R)-3-tetradecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1 0-((3R)-3-hexadecanoyloxytetradecanoyl)-o-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-((3R)-3-hexadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-hexadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-((3R)-3-hexadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1 -0-((3R)-3-hexadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-((3R)-3-octadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-octadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-((3R)-3-octadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosa noyloxytetradecanoyl}-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]- L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-eicosanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-eicosanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eeicosanoyloxytetradecanoyl}-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosanoyloxytetradecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosanoyloxytetrdecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(( 3R)-3-eicosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-eicosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-eicosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-eicosanoyloxytetradecanoyl)-6-0-tetradecanoyl1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-({3R)-3-eicosanoyloxytetradecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-eicosanoyloxytetradecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-1-actoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-docosanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl---isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxytetradecanoyl)-6-0-decanoyl-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxytetradecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxytetradecanoyl-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxytetradecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxytetradecanoyl)-6-0-dodecanoyl-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxytetradecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxytetradecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxytetradecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-tetracosanoyloxytetradecaoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-((3R)-3-tetracosanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-{(3R)-3-tetracosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-((3R)-3-tetracosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-{2-dodecyltetradecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-(2-dodecyltetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-(2-dodecyltetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-[2-dodecyl-tetradecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-[2-dodecyltetradecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecyltetradecanoyl)-6-0-octadecanoyl-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecyltetradecanoyl}-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-(2-dodecyltetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-(2-dodecyltetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecyl-tetradecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-gluco-pyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecyltetradecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-[2-dodecyltetradecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-gluco pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-hexadecyloctadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-2-hexadecyloctadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-(2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-(2-hexadecyloctadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-hexadecyloctadecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-[2-hexadecyloctadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-hexadecyloctadecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-hexadecyloctadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-(2-hexadecyloctadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-(2-hexadecyloctadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-hexadecyl-octadecanoyl)-6-0-tetradecanoyl-1-thio-8-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-(2-hexadecyloctadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-hexadecyloctadecanoyl}-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-octadecyleicosanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-(2-octadecyleisocanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-(2-octadecyleicosanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-octadecyleicosanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-(2-octadecyleicosanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-(2-octadecyleicosanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-octadecyleicosanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-(2-octadecyleicosanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-[2-octadecyleicosanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-octadecyleicosanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-(2-octadecyleicosanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-(2-octadecyleicosanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-[2-Acetamido-2,3-dideoxy-1-0-(2-dodecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-(2-dodecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
.N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-(2-dodecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecylhexadecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecylhexadecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecylhexadecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-(2-dodecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-(2-dodecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-{2-dodecylhexadecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecylhexadecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-[2-dodecylhexadecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecyloctadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-(2-dodecyloctadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lacto-yl]-L- alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-(2-dodecyloctadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecyloctadecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecyloctadecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecyloctadecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecyloctadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-(2-dodecyloctadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-(2-dodecyloctadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecyloctadecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecyloctadecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecyloctadecanoyl)-6-0-octadecanoyl-1-thio-8-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecyleicosanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-(2-dodecyleicosanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl- D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-(2-dodecyleicosanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecyleicosanoyl)-6-0-tetradecnaoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecyleicosanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-(2-dodecyleicosanoyl)-6-0-octadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecyl-eicosanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-(2-dodecyleicosanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-(2-dodecyleicosanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-{2-dodecyleicosanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-1actoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(2-dodecyeicosanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-[2-dodecyleicosanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R}-3-dodecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-docanoyl-1-0-((3R)-3-dodecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-dodecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-(2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxydodecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxydodecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxydodecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-docanoyl-1-S-((3R)-3-dodecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-dodecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxydodecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxydodecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxydodecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-L glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-tetradecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-tetadecanoyloxydodecanoyl)-.alpha.-D-glucopyrano-s-3- yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-tetradecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-0-((3R)-3-ttradecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-((3R)-3-tetradecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-tetradecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-tetradecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-tetradecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-tetradecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl- 1-S-((3R)-3-tetradecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-[(3R)-3-tetradecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R)-3-tetradecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-[(3R)-3-hexadecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-hexadecanoyloxydodecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-hexadecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-[(3R)-3-hexadecanoyloxydodecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-c. 1-0-{(3R)-3-hexadecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-hexadecanoyloxydodecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-hexadecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-hexadecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-hexadecanoyloxydodecanoyl)-1-thio-.beta.-D-gluco- pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-hexadecanoyloxydodecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-((3R)-3-hexadecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(( 3R)-3-hexadecanoyloxydodecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-octadecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-octadecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-octadecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-octadecanoyloxydodecanoyl}-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-((3R)-3-octadecanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-octadecanoyloxydodecanoyl)-.alpha.-D-gluco-pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3 -octadecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-octadecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-octadecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos- 3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-octadecanoyloxydodecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-((3R)-3-octadecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R)-3-octadecanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-eicosanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-eicosanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosanoyloxydodecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosanoyloxydodecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-[(3R)-3-eicosanoyloxydodecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-eicosanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-eicosanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-eicosanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-eicosanoyloxydodecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-eicosanoyloxydodecanoly)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-eicosanoyloxydodecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxydodecanol)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-.alpha.- 6-0-decanoyl- -1-0-((3R)-3-docosanoyloxydodecanoyl)-.alpha. -D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxydodecanoyl)-6-0-dodecanoyl-.alpha. -D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine-methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxydodecanoyl)-6-0-tetradecanoyl-.alpha. -D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-[(3R)-3-docosanoyloxydodecanoyl)-6-0-hexadecanoyl-.alpha. -D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-{(3R)-3-docosanoyloxydodecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1- S-((3R)-3-docosanoyloxydodecanoyl)-1-thio-0 -D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxydodecanoyl)-6-0-dodecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxydodecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-[(3R)-docosanoyloxydodecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxydodecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-tetracosanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-tetracosanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-tetracosanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-tetracosanoyloxydodecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-((3R)-3-tetracosanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-tetracosanoyloxydodecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-tetracosanoyloxydodecanoyl)-1-thio-.sym.-D-glucopyranos-3yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-tetracosanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl- 1-S-((3R)-3-tetracosanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-({3R)-3-tetracosanoyloxydodecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-((3R)-tetracosanoyloxydodecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R)-3-tetracosanoyloxydodecanoyl)-1-thio-.beta.-D-L glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-dodecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R}-3-dodecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3- dodecanoyloxyhexadecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-(2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxyhexadecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-dodecanoyloxyhexadecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-r yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-dodecanoyloxyhexadecanoyl}-1-thio-.beta.-D-glucoL pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-(3R)-3-dodecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-(3R)-3-dodecanoyloxyhexadecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxyhexadecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-dodecanoyloxyhexadecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-tetradecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-tetradecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-L 3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-tetradecanoyloxyhexadecanoyl)-.alpha.-D-glucoL pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-0-[(3R)-3-tetradecanoyloxyhexadecanoyl)-.alpha.-D-glucoi pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl- 1-0-((3R)-3-tetradecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-tetradecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-[(3R)-3-tetradecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-L 3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-tetradecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-tetradecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-S-((3R)-tetradecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl- 1-S-((3R)-3-tetradecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R)-3-tetradecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-hexadecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-hexadecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-hexadecanoyloxyhexadecanoyl)-.alpha.-D-glucoL pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-hexadecanoyloxyhexadecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl- 1-0-((3R)-3-hexadecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-([3R)-3-hexadecanoyloxyhexadecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-hexadecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-hexadecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-hexadecanoyloxyhexadecanoyl)-1-thio-.beta.-D-L glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-hexadecanoyloxyhexadecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-[(3R)-3-hexadecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isogluta mine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-hexadecanoyloxyhexadecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-octadecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-octadecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-L 3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R)-3-octadecanoyloxyhexadecanoyl)-.alpha.-D-glucoL pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-octadecanoyloxyhexadecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-((3R)-3-octadecanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-octadecanoyloxyhexadecanoyl)-.alpha.-D-gluco-pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-octadecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-octadecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucoL pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-octadecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-octadecanoyloxyhexadecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-L glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-((3R)-3-octadecanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-[(3R)-3-octadecanoyloxyhexadecanoyl)-1-thio-.beta.-D- glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-eicosanoyloxyhexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R}-3-eicosanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-- 3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosanoyloxyhexadecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucoL pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosanoyloxyhexadecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucoL pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-eicosanoyloxyhexadecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-eicosanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-eicosanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucoL pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-eicosanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-{(3R)-3-eicosanoyloxyhexadecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-eicosanoyloxyhexadecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-eicosanoyloxyhexadecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-docosanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxyhexadecanoyl)-6-0-dodecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-[(3R)-3-docosanoyloxyhexadecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucoL pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxyhexadecanoyl)-6-0-hexadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-docosanoyloxyhexadecanoyl)-6-0-octadecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-[(3R)-3-docosanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-docosanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxyhexadecanoyl)-6-0-dodecanoyl-1-thio-.beta.-D-L glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxyhexadecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxyhexadecanoyl)-6-0-hexadecanoyl-1-thio-.beta.-D-L glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-docosanoyloxyhexadecanoyl)-6-0-octadecanoyl-1-thio-.beta.-D-r glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-tetracosanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-((3R)-3-tetracosanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-0-((3R}-3-tetracosanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-tetracosanoyloxyhexadecanoyl)-6-0-tetradecanoyl-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-0-((3R)-3-tetracosanoyloxyhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-tetracosanoyloxyhexadecanoyl}-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-tetracosanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-3-tetracosanoyloxyhexadecanoyl)-1-thio-.beta.-D-gluco pyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-dodecanoyl-1-S-((3R)-3-tetracosanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-tetracosanoyloxyhexadecanoyl)-6-0-tetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-hexadecanoyl-1-S-((3R)-3-tetracosanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester and
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R)-3-tetracosanoyloxyhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methylester.
The compounds of the present invention can be basically prepared by the following process. ##STR10## In the formulae, X is OH or SH; R.sub.1 and R.sub.2 are defined as above.
The above mentioned process consists of two acylation steps (the acylations at 6th and 1st positions of the glucopyranose moiety) and one deacetonation step.
The two acylation steps can be conducted by reacting a compound of the formula (II) or (I') with a specific acylating agent (R.sub.2 H, R.sub.3 H or its reactive derivative). These steps are generally carried out in an anhydrous organic solvent (for example, dimethylformamide or dioxane) and at room temperature or a slightly elevated temperature. When R.sub.2 H or R.sub.3 H (a free acid) is used, it is conducted in the presence of an appropriate condensing agent (for example, dicyclohexylcarbodiimide, N-cyclohexyl-N'-morpholinoethylcarbodiimide, N-cyclohexyl-N'-(4-diethylaminocyclohexyl)-carbodiimide or N,N'-diethylcarbodiimide). Examples of reactive derivatives of R.sub.2 H or R.sub.3 H are conventional reactive derivatives used in acylation, such as mixed acid anhydrides, active esters, acid halides and the like. The deacetonating step can be readily conducted under an acid hydrolysis condition (e.g., using 80% acetic acid aqueous solution) at a slightly elevated temperature.
The compounds of the formula (II) are known or can be readily prepared by known methods.
The compounds obtained by the above process may be purified by a conventional method such as a column chromatography using alumina or silica gel, recrystallization and the like.
The compounds of the formula (I) of the present invention have an action for enhancing function of cells relevant to in vivo immune response and an action for increasing the number of said cells, and hence they are useful as an immunoregulating agent. The immunoregulating agent of the present invention can be used to enhance in vivo activities of vaccines such as BCG vaccine, hepatitis vaccine, influenza virus vaccine or the like, various antibacterial agents or anti-tumor agents.
The immunoregulating composition of the present invention comprises a compound of the formula (I) and a pharmaceutically acceptable carrier. The composition may be any dosage form for oral and parenteral administrations.
The compositions for oral administration are generally dosage forms such as powders, tablets, emulsions,capsules, granules and liquid prepartions (including liquid extracts, syrups and the like).
Examples of carriers for powders or other orally administrable solid preparations include lactose, starch, dextrin, calcium phosphate, calcium carbonate, synthetic or natural aluminium silicate, magnesium oxide, dried aluminium hydroxide, magnesium stearate, sodium bicarbonate, dried yeast and the like, and those for liquid preparations include water, glycerine, propylene glycol, simple syrup, ethanol, fatty oil, ethylene glycol, polyethylene glycol, sorbitol and the like. A typical example of the composition for parenteral administration is an injection. Liquid carriers for the injection include sterile distilled water. When a compound of the formula (I) is less soluble in water, an appropriate solubilizer is used. Each of the above preparations can be prepared by conventional methods.
When the compounds of the formula (II) of the present invention are used for enhancement of antitumor agents, they may be orally or parenterally administered to an adult human in an amount of 150 to 250.mu.g/day in one dose. When used for enhancement of vaccines, they may be administered to an adult human in an amount of 0.5 to 2.0 mg/1 to 2 weeks in one dose. For treatment of hepatitis, they may be orally or parenterally administered to an adult human 1 to 3 times for 3 months in an amount of 0.5 to 2.0 mg in one dose. For enhancement of antibacterial agents, they may be used to an adult human in an amount 20 to 100.mu.g/day in one dose.
The immunoregulating agents of the present invention may be generally used by formulating themselves only as described above. But they may be formulated together with an agent to be enhanced its action.
Further, the immunoregulating agents of the present invention can be used for not only humans but also other mammals such as pigs, bovines, sheeps, dogs, and cats.

The present invention is illustrated with following examples.
EXAMPLE 1
N-[2-0-i2-Acetamido-2,3-dideoxy-1-0-[2-tetra-decylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L--alanyl-D-isoglutamine methylester
The compound of the formula (III) wherein R.sub.1 is 2-tetradecylhexadecanoyloxy group (279.4 mg, 0.281mmol) was dissolved in 80% acetic acid aqueous solution (8 ml) and the resultant was allowed to stand for 2 hours at 45.degree. C. After confirming the completion of the reaction with T.L.C.(CH.sub.2 Cl.sub.2 :MeOH=10:1), the resultant was concentrated under reduced pressure to obtain quantitatively the title compound (266.2 mg).
mp : 147.0.degree.-148.0.degree. C.
[.alpha.].sub.D.sup.25 : +44.38.degree. (c=1.050, CH.sub.2 Cl : MeOH=1 : 1)
IR .gamma.max(KBr)cm.sup.-1 :3350, 2930, 2850, 1740, 1650, 1520
NMR(CD.sub.3 OD--CHCl.sub.3).delta.(ppm) : 0.88(t,6H,J=6.6 Hz), 1.26(s,48H), 1.38-1.43(m,6H), 1.51-1.62(m,4H), 1.93(s,3H), 3.70(s,3H), 6.16(d,1H,J=4.0 Hz)
EXAMPLE 2
N-{2-0-2-Acetamido-2,3-dideoxy-1-S-(2-tetradecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl]-D-lactoyl}-L-alanyl-D-isoglutamine methylester
The compound of the formula (III) wherein R.sub.1 is 2-tetradecylhexadecanoylthio group (133.7 mg) was dissolved in 80% acetic acid aqueous solution (15 ml), which was allowed to react for 2 hours at 45.degree. C. After confirming the completion of the reaction with T.L.C., the resultant was concentrated under reduced pressure and crystallized from ether to obtain quantitatively the title compound (127.0 mg, crystals).
mp:130.0.degree.-131.0.degree. C. [.alpha.].sub.D.sup.25 :+46.79.degree. (c=1,201, CH.sub.2 Cl.sub.2 :MeOH=1:1)
IR.gamma.max(KBr)cm.sup.-1 :3300, 2920, 2850, 1720, 1630, 1530
EXAMPLE 3
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3- tetradecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (III wherein R.sub.1 is 3-tetradecanoyloxytetradecanoyloxy group (409.1 mg, 0.411mmol) was dissolved in 80% acetic acid aqueous solution 15 ml and allowed to stand for an hour at 45.degree. C. In the same manner as that in Example 1, the title compound was quantitatively obtained (386.9 mg).
mp : 133.8.degree.-134.6.degree. C. [.alpha.].sub.D.sup.25 :+44.74.degree. (c=1.180, CHCl.sub.3 MeOH=1:1)
IR .gamma.max(KBr)cm.sup.-1 : 3700-3140, 2930, 2850, 1740, 1250, 1630, 1540
NMR(CDCl.sub.3).delta.:0.89(t,6H,J=2.2 Hz), 1.27(m,36H), 1.43(m,6H), 1.60(m,4H), 2.00(s,3H), 2.10-2.30[m,4H), 2.44-2.67(m,6H), 3.68(s,3H), 5.31(m,1H), 6.05(d,1H)
EXAMPLE 4
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-[[3R)-3-tetradecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (III) wherein R.sub.1 is 3-tetradecanoyloxytetradecanoylthio group (580.1 mg, 0.5808mmol) was dissolved in 80% acetic acid aqueous solution 12 ml) and allowed to stand for an hour at 45.degree. C. After confirming the completion of the raction with T.L.C. (CH.sub.2 Cl.sub.2 :MeOH=10 1), the resultant was concentrated under reduced pressure. The resulting syrup was lyophilized to obtain quantitatively the title compound (555.2 mg, crystals).
mp : 110.degree.-111.degree. C.
[.alpha.].sub.D.sup.25 :+26.68.degree. (c=0.787, CH.sub.2 Cl.sub.2 :MeOH=2 1)
IR .gamma.max(KBr)cm.sup.-1 : 3650-3130, 3300, 2940, 2860, 1740, 1650, 1550,
NMR(CDCl.sub.3 --CD.sub.3 OD).delta.:0.88 (t,6H,J=6.6 Hz), 1.25(m,36H), 1.35 (d,3H,J=7.0 Hz), 1.39 (d,3H,J=7.3 Hz), 1.43-1.58 (m,4H), 1.93(s,3H), 1.93-2.04 (m,2H), 2.09-2.87(m,6H), 3.71(s,3H), 4.05(t,1H,J= 10.4 Hz), 4.28-4.33(m,1H), 4.31(q,1H,J=7.0 Hz), 4.38-4.43 (m,1H), 5.12(d,1H,J=11.0 Hz) 5.17-5.26(m,1H)
EXAMPLE 5
N-[2-0-i2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0-(2-tetradecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I) wherein R.sub.1 is 2-tetradecylhexadecanoyloxy group (143.3 mg, 0.150mmol) was dissolved in a mixture of dry dioxane (1.3 ml.) and dry N,N-dimethylformamide (DMF, 1.3 ml). To the solution were added decanoic acid (29.6 mg, 0.180mmol), dicyclohexylcarbodiimide (DCC, 61.7 mg, 0.300mmol) and dimethylaminopyridine (DMAP, 9.1 mg, 0.075mmol), and the resultant was stirred for 14 hours at room temperature. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure. The resulting syrup was subjected to a column chromatography [Wakogel.RTM.C-200 eluted with CH.sub.2 CL.sub.2 /MeOH ((a) 150:1 and (b) 20:1)] and the eluate eluted with the eluent (b) was concentrated under reduced pressure. The resultant syrup was subjected to a column chromatography [active alumina 90 eluted with CH.sub.2 Cl.sub.2 /MeOH ((a') 150:1 and (b') 20:1)], to remove DMAP and the eluate eluted with eluent (b') gave the title compound (121.3 mg, yield: 72.6%).
m;:116.31.degree.-117.0.degree. C.
[.alpha.].sub.D.sup.25 :+42.56.degree.(C=0.726, CHCl.sub.3 :MeOH=2:1)
IR.gamma.max(KBr)cm.sup.-1 :3650-3150, 2940, 2870 1740, 1650, 1540
NMR(CDCl.sub.3).delta.:0.88(t,6H,J=6.8 Hz), 0.92(t,3H,J=7.1 Hz), 1.25(m,62H), 1.39(d,3H,J=6.6 Hz), 1.41(d,3H,J=6.6 Hz), 1.51-1.60(m,6H), 1.90-2.23(m,2H), 1.94(s,3H), 2.33(t,2H,J-7.5 Hz), 2.39-2.50(m,3H), 3.69(s,3H), 6.18(d,1H,J=3.7Hz)
EXAMPLE 6
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-0-(2-tetradecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 2-tetradecylhexadecanoyloxy group (1.39.7 mg, 0.147 mmol) is dissolved in a mixture of dry dioxane (2 ml) and dry DMF (2 ml). To the solution were added tetradecanoic acid (40.0 mg, 0.176 mmol), DCC(60.2 mg, 0.294 mmol) and DMAP(8.9 mg, 0.074 mmol). The resultant was stirred for 12 hours at room temperature and then treated in the same manner as that in Example 5 to obtain the title compound (105.4 mg, yield: 61.7%).
mp:116.8.degree.-117.7.degree. C.
[.alpha.].sub.D.sup.25 :+29.22.degree.(c=1.054, CH.sub.2 Cl.sub.2)
IR.gamma.max(KBr)cm.sup.-1 :3700-3100, 2940, 2860, 1740, 1660, 1540
NMR(CDCl.sub.3).delta.:0.88(t,9 H,J=6.4 Hz), 1.25(m,7H) 1.38)d,3H, J=6.6 Hz), 1.41(d,3H, J=7.3 Hz), 1.49-1.60(m,6H), 1.93(s,3H), 2.03-2.21(m,2H), 2.32(t,2H,J=7.7 Hz), 2.38-2.74(m,3H), 3.68(s,3H), 6.17(d,1H,J=3.7 Hz)
ESAMPLE 7
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-(2-tetradecylhexadecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 2-tetradecylhexadecanoyloxy group (122.7 mg, 0.129 mmol) was dissolved in a mixture of dry dioxane (1.5 ml) and dry DMF(0.5 ml). To the solution were added octadecanoic acid (44.5 mg, 0.155 mmol), DCC(53.7 mg, 0.258 mmol) and DMAP(7.9 mg, 0.065 mmol). The resultant was stirred for 14 hours and then treated in the same manner as that in Example 5 to obtain the title compound(119.0 mg, yield:75.6%).
mp:118.7.degree.-102.0.degree. C.
[.alpha.].sub.D.sup.25 :+39.45.degree.(c=0.621, CHCl.sub.3 :MeOH=2:1)
IR.gamma.max(KBr)cm.sup.-1 :3650-3150, 2930, 2860, 1740, 1650, 1540
NMR(CDCl.sub.3).delta.:0.88(t,9H,J=6.6 Hz), 1.25(m,78H), 1.39(d,3H,J=6.6 Hz), 1.41(d,3H,J=6.6 Hz), 1.49-1.60(m,6H), 1.94(s,3H), 1.90-2.26(m,2H), 2.32(t,2H,J=7.3 Hz), 2.39-2.50(m,3H), 3.69(s,3H), 6.18(d,1H,J=3.7 Hz)
EXAMPLE 8
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-(2-tetradecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3--yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 2-tetradecylhexadecanoylthio (128.4 mg, 0.134 mmol) was dissolved in a mixture of dry dioxane (1.5 ml) and dry DMF (1.0 ml). To the solution were added decanoic acid (27.4 mg, 0.161 mmol), DCC(54.6 mg, 0.268 mmol) and DMAP(8.1 mg, 0.067 mmol). The resultant was stirred for 6.5 hours at room temperature. After confirming the completion of the reaciton with T.L.C. (10:1), the resultant was lyophilized and subjected to a column chromatography [Wakogel.RTM. C-200 eluted with CH.sub.2 Cl.sub.2 /MeOH ((a) 150:1 and (b) 50:1)]. The elute eluted with the eluent (b) gave the title compound (99.6 mg, yield: 66.8%).
mp:98.6.degree.-99.4.degree. C.
[.alpha.].sub.D.sup.25 : +17.69.degree.(c=0.797, CH.sub.2 Cl.sub.2 :MeOH=2:1)
IR.gamma.max(KBr)cm.sup.-1 :3500-3200, 2950, 2880, 1750, 1640, 1560
NMR(CDCl.sub.3 --CD.sub.3 OD).delta.: 0.88(t,6H,J=6.6 Hz), 0.92(t,3H,J=7.1 Hz), 1.25(m,56H), 1.34(d,3H,J=6.6 Hz), 1.40(d,3H,j=7.0 Hz), 1.58-1.71(m,6H), 1.90(s,3H), 1.94-2.24(m,2H), 2.33(t,2H,J=7.5 Hz), 2.42-2.52(m,3H), 3.69(s,3H), 5.11(d,1H,J=10.6 Hz)
EXAMPLE 9
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-S-(2-tetradcylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 2-tetradecylhexadecanoylthio group (125.0 mg, 0.131 mmol) was dissolved in a mixture of dry dioxane (1.5 ml) and dry DMF (1.0 ml). To the solution were added tetradecanoic acid (353.3 mg, 0.157 mmol), DCC(53.1 mg, 0.262 mmol) and DMAP (7.9 mg, 0.066 mmol). The resultant was stirred for 3 hours at room temperature and then treated in the same manner as that in Example 8 to obtain the title compound (1.25.8 mg, yield: 82.5%).
mp:99.0.degree.-100.4.degree. C.
[.alpha.].sub.D.sup.25 :+2.13.degree.(c=2.16, CH.sub.2 Cl.sub.2)
IR.gamma.max(KBr)cm.sup.-1 :3650-3200, 2930, 2860, 1740, 1650, 1550
NMR(CDCl.sub.3).delta.:0.85-0.95(m,9H), 1.25(m,68H), 1.36(d,3H,J=6.6 Hz), 1.41(d,3H,J=7.3 Hz), 1.47-1.76(m,6H), 1.88-2.32(m,2H), 1.94(s,3H), 2.35(t,2H,J=7.9 Hz), 2.47-2.53(m,3H), 3.70(s,3H), 5.12(d,1H,J=10.3 Hz)
EXAMPLE 10
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-(2-tetradecylhexadecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 2-tetradecylhexadecanoylthio (122.4 mg, 0.128 mmol) was dissolved in a mixture of dry dioxane (1.5 ml) and dry DMF (1.0 ml). To the solution were added octadecanoic acid (43.0 mg, 0.145 mmol), DCC(52.0 mg, 0.245 mmol) and DMAP (7.7 mg, 0.064 mmol). The resultant was stirred for 4 hours at room temperature and treated in the same manner as that in Example 8 to obtain the title compound (102.7 mg, yield:65.6%).
mp:99.3.degree.-101.0.degree. C.
[.alpha.].sub.D.sup.25 :+2.06.degree. (c=0.376, CH.sub.2 Cl.sub.2 :MeOH=2:1)
IR.gamma.max(KBr)cm.sup.-1 :3600-3150, 2920, 2840, 1740, 1640, 1540
NMR(CDCl.sub.3 -CD.sub.3 OD).delta.:0.88(t,9H,J=6.6 Hz), 1.26(m,76H), 1.35(d,3H,J=6.6 Hz), 1.40(d,3H,J=7.3 Hz), 1.58-1.61(m,6H), 1.88(s,3H), 1.92-2.26(m,2H), 2.33(t,2H,J.ltoreq.7.7 Hz), 2.41-2.55(m,3H), 3.69(s,3H), 4.40(q,1H), 5.10(d,1H,J=11.0 Hz)
EXAMPLE 11
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-0((3R)-3-tetradecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 3-tetradecanoyloxytetradecanoyloxy group (116.9 mg, 0.121 mmol) was dissolved in a mixture of dioxane (1.5 ml) and dry DMF (0.5 ml). To the solution were added decanoic acid (24.3 mg, 0.145 mmol), DCC (48.4 mg, 0.242 mmol) and DMAP (7.2 mg, 0.161 mmol). The resultant was stirred for 8 hours at room temperature. After confirming, the completion of the reaction with T.L.C. (CH.sub.2 Cl.sub.2 :MeOH=10:1), the resultant was concentrated under reduced pressure. The resulting syrup was subjected to a column chromatography [Wakogel.RTM. C-200 eluted with CH.sub.2 Cl.sub.2 /MeOH ((a) 150:1 and (b) 35:1)]. The eluate eluted with the eluent (b) gave the title compound (80.4 mg, yield:59.6%).
mp:72.0.degree.-72.8.degree. C.
[.alpha.].sub.D.sup.25 :+27.86.degree.(c=0.804, Ch.sub.2 Cl.sub.2)
IR.gamma.max(Film)cm.sup.-1 :3700-3100, 2930, 2850, 1740, 1650, 1540
NMR(CDCl.sub.3).delta.:0.88(t,9H,J=6.6 Hz), 1.25-1.27(m,48H), 1.43(d,3H, J=6.6 Hz) 1.45(d,3H,J=7.0 Hz), 1.61(m,6H), 2.00(s,3H), 2.04-2.24(m,2H), 2.30(t,2H, J=7.5 Hz), 2.32-2.67(m,6H), 3.69(s,3H), 4.21(q,1H,J=6.6 Hz), 5.29(m,1H), 6.05(d,1H,J=3.3 Hz)
EXAMPLE 12
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-0-((3R)-3-tetradecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 3-tetradecanoyloxytetradecanoyloxy (108.6 mg, 0.15 mmol) was dissolved in a mixture of dry dioxane (1.5 ml) and dry DMF (0.5 ml). To the solution were added tetradecanoic acid (30.1 mg, 0.137 mmol), DCC(45.3 mg, 0.228 mmol) and DMAP (6.7 mg, 0.057 mmol). The mixture was allowed to react for 14 hours at room temperature. The resultant was treated in the same manner as that in Example 11 to obtain the title compound (99.1 mg, yield: 74.6%).
mp:72.5.degree.-73.6.degree. C.
[.alpha.].sub.D.sup.25 :+26.51.degree.(c=1.388CH.sub.2 Cl.sub.2)
IR.gamma.max(film)cm.sup.-1 :3700-3150, 2930, 2850, 1740, 1660, 1540
NMR(CDCl.sub.3).delta.:0.88(t,9H,J=6.6 H), 1.25-1.38(m,56H), 1.43(d,3H,J=6.6 Hz), 1.45(d,3H,J=7.0 Hz), 1.60(m,6H), 1.99(s,3H), 2.06-2.24(m,2H), 2.30(t,2H,J=7.5 Hz), 2.32-2.66(m,6H), 3.69(s,3H), 4.21(q,1H,J=7.0 Hz), 5.30(m,1H), 6.05(d,1H,J=3.3 Hz)
EXAMPLE 13
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-tetradecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 3-tetradecanoyloxytetradecanoyl group (108.8 mg, 0.114 mmol) was dissolved in a mixture of dry dioxane (1.5 ml) and dry DMF (0.5 ml). To the solution were added octadecanoic acid (37.6 mg, 0.137 mmol), DC (45.4 mg, 0.228 mmol) and DMAP (6.7 mg, 0.057 mmol). The resultant was stirred for 14 hours at room temperature and then treated in the same manner as that in Example 11 to obtain the title compound (95.6 mg, yield:68.5%).
mp:68.1.degree.-69.0.degree. C.
[.alpha.].sub.D.sup.25 :+26.15.degree.(c=1.338, CH.sub.2 Cl.sub.2) IR.gamma.max(film)cm.sup.-1 :3700-3150, 2930, 2850, 1740, 1650, 1540
NMR(CDCl.sub.3).delta.:0.88(t,9H,J=6.6 Hz), 1.25-1.39(m,64H), 1.43(d,3H,J=6.6 Hz), 1.44(d,3H,J=7.0 Hz), 1.58-1.60(m,6H), 1.99(s,3H), 2.02-2.22(m,2H), 2.30(t,2H,J=7.5 Hz), 2.32-2.67(m,6H), 3.69(s,3H0, 4.21(q,1H,J=6.6 Hz), 5.30(m,1H), 6.05(d,1H,J=3.3 Hz)
EXAMPLE 14
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-decanoyl-1-S-((3R)-R-tetradecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I) wherein R.sub.1 is 3-tetradecanoyloxytetradecanoylthio (239.2 mg, 0.250 mmol) was dissolved in a mixture of dry dioxane (0.5 ml) and dry DMF (0.5 ml). To the solution were added decanoic acid (51.6 ml, 0.300 mmol), DCC (102.9 mg, 0.50 mmol) and DMAP (15.2 mg, 0.499 mmol), and the resultant was stirred for 2 hours at room temperature. After confirming the completion of the reaction with T.L.C. (CH.sub.2 Cl.sub.2 :MeOH=10:1), DC urea of a reaction by-product was filtered off and washed with dioxane. The filtrate and washings were combined and then lyophilized. The amorphous material thus obtained was subjected to a column chromatography [Wakogel.RTM. C-200 eluted with CH.sub.2 Cl.sub.2 /MeOH ((a) 200:1, (b) 70:1, (c) 60:1 and (d) 40:1)]. The eluate eluted with the eluent (c) gave the title compound (111.6 mg, yield: 40.2%).
mp:138.6.degree.-139.9.degree. C.
[.alpha.].sub.D.sup.25 :+17.09.degree. (c=0.70, CH.sub.2 Cl.sub.2 :MeOH=2:1)
IR.gamma.max(film)cm.sup.-1 :3650-3020, 3250, 2930, 2850, 1740, 1660, 1540
NMR(CDCl.sub.3).delta.:0.87(t,9H,J=5.7 Hz), 1.25(m,52H), 1.39(d,3H,J=6.6 Hz), 1.58(m,6H), 1.95(s,3H), 2.10-2.28(m,2H), 2.34(6,2H,J=7.7 Hz), 2.47-2.91(m,6H), 3.69(s,3H), 5.13(d,1H,J=11.0 Hz), 5.11-5.21(m,1H)
EXAMPLE 15
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-tetradecanoyl-1-S-((3R)-3-tetradecanoyloxytetradecanoyl-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 3-tetradecanoyloxytetradecanoylthio (206.5 mg, 0.215 mmol) was dissolved in dry dioxane (0.5 ml) and dry DMF (0.5 ml). To the solution were added tetradecanoic acid (59.0 mg, 0.259 mmol), DCC (88.9 mg, 0.431 mmol) and DMAP (13.1 mg, 9.1077 mmol). The resultant was stirred for 2.5 hours at room temperature and then treated in the same manner as that in Example 14 to obtain the title compound (95.6 mg, yield: 38.0%).
mp:136.1.degree.-137.7.degree. C.
[.alpha.].sub.D.sup.25 : +17.57.degree.(c=0.956, CH.sub.2 Cl.sub.2 :MeOH=2:1)
IR.gamma.max(film)cm.sup.-1 :3650-3120, 3300, 2930, 2860, 1740, 1640, 1540
NMR(CDCl.sub.3).delta.:0.88(t,9H,J=6.6 Hz), 1.25(m,56H), 1.39(d,3H,J=7.0 Hz), 1.42 (d,3H,J=7.0 Hz), 1.57(m,6H), 1.97(s,3H), 2.01-2.28(m,2H), 2.34(t,2H,J=7.7 Hz), 3.71(s,3H), 5.13(d,1H,J=11.0 Hz), 5.11-5.23(m,1H)
EXAMPLE 16
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R)-3-tetradecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 3-tetradecanoyloxytetradecanoylthio (203.2 mg, 0.212 mmol) was dissolved in a mixture of dry dioxane (0.5 ml) and dry DMF (0.5 ml). To the solution were added octadecanoic acid (63.1 mg, 0.254 mmol), DCC (87.5 mg, 0.424 mmol) and DMAP (12.9 mg, 0.106 mmol). The resultant was stirred for 3 hours at room temperature and then treated in the same manner as that in Example 14 to obtain the title compound (112.2 mg, yield:43.2%).
mp:133.7.degree.-134.5.degree. C.
[.alpha.].sub.D.sup.25 :+17.46.degree. (c=1.122, CH.sub.2 Cl.sub.2 :MeOH=2:1)
IR.gamma.max(film)cm.sup.-1 :3700-3150, 3320, 2960, 2900, 1750, 1680, 1580
NMR(CDCl.sub.3).delta.:0.87(6,9H,J=5.5 Hz), 1.25(m,6.6H), 1.39(d,3H,J=5.9 Hz), 1.57(m,6H), 1.95(s,3H), 1.95-2.18(m,2H), 2.25-2.90(m,6H), 2.38(t,2H,J=7.1 Hz), 3.69(s,3H), 5.13(d,1H,J=11.0 Hz), 5.11-5.20(m,1H)
EXAMPLE 17
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-hexadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (II) wherein R.sub.1 is 3-hexadecanoyloxytetradecanoyloxy (408.8 mg, 0.410 mmol) was dissolved in 80% acetic acid aqueous solution (15 ml), which was allowed to stand for 1.5 hours at 45.degree. C. In the same manner as that in Example 4, the title compound (391.7 mg) was quantitatively obtained from the above solution.
m.p.:134.2.degree.-135.5.degree. C.
[.alpha.].sub.D.sup.25 :+47.38.degree. (c=0.878, CH.sub.2 Cl.sub.2 :MeOH=1:1)
IR.gamma.max(cm).sup.-1 :3700-3100(OH), 3300(NH), 2930, 2850(CH), 1740(ester), 1650, 1530(amido)
NMR(DCDl.sub.3).delta.:0.88(t,9H,JMeCH.sub.2 6 Hz, 3MeCH.sub.2), 1.25(m,40H,30 CHz), 1.42(d,3H,J.sub.MeCH 7.3 Hz, Mec of Ala), 1.45(d,3H,J.sub.MeCH 7.3 Hz,Hec of Lac), 1.57-1.60(m,6H,3MeCh.sub.2), 1.95-2.17(m,2H,CH.sub.2 CH of Gln), 2.00(s,3H,AcN), 2.30(t,2H,JCH.sub.2 CH.sub.2 7.5 Hz,CH.sub.2 CO of Gln), 2.37-2.66(m,6H,3CH.sub.2 CO), 3.68(S,3H,COOMe), 5.30-5.42(m,1H,H--3 of C.sub.17 --O--C.sub.16), 6.03(d,1H,J.sub.1.2,3.3 Hz,H--1),
EXAMPLE 18
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0octadecanoyl-1-0-((3R)-3-hexadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 3-hexadecanoyloxytetradecanoyloxy (191.1 mg, 0.200 mmol) was dissolved in a mixture of dry dioxane (3.0 ml) and dry DMF (1.0 ml). To the solution were added octadecanoic acid (74.0 mg, 0.260 mmol), DDC(82,5 mg, 0.400 mmol) and DMAP (12.2 mg, 0.100 mmol). The resultant was stirred for 16 hours at room temperature. In the same manner as that in Example 11, the title compound (193.1 mg, yield:78.9%) was obtained.
mp : 69.5.degree.-71.0.degree. C.
[.alpha.].sub.D.sup.25 :+40.69.degree. (C=l.504, CH.sub.2 Cl.sub.2 :MeOH=2 1)
IR .gamma.max(cm.sup.-1) : 3700-3130(OH), 3300(NH), 2930, 2860(CH), 1740(ester), 1660, 1540(amido),
NMR(CDCl.sub.3) 0.88(t,9H,JMeCH.sub.2 6.6 Hz,3MeCH.sub.2), 1.25(m,68H,34CH.sub.2), 1.43(d,3H,JMeCH5.9 Hz,MeC of Ala), 1.45(d,3H,JMeCH5.9 Hz,MeC of Lac), 1.60(m,6H,3MeCH.sub.2), 1.99(s,3H,AcN), 2.19-2.66(m,8H,CH.sub.2 CH of Gln,3CH.sub.2 CO), 2.35[t,2H,JCH.sub.2 CH.sub.27.7 Hz,CH.sub.2 CO of Gln), 3.69(s,3H,COOMe), 5.30(m,1H,H--3 of C.sub.14 OC.sub.16), 6.05(d,1H,J.sub.1.2 2.9 Hz,H--1)
EXAMPLE 19
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-hexadecaonyloxytetradecanoyl-1-thio-.beta.-D-qlucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (III) wherein R.sub.1 is 3-hexadecanoyloxytetradecanoylthio (586.6 mg, 0.580mmol) was dissolved in 80% acetic acid aqueous solution (12 ml), which was allowed to stand for an hour at 45.degree. C. In the same manner as that in Example 4, the title compound 563.4 mg) was quantitatively obtained.
mp : 94.6.degree.-95.8.degree. C.
[.alpha.].sub.D.sup.25 :+28 06(C=1.112, CH.sub.2 Cl.sub.2.:MeOH=1:1)
IR .gamma.max(cm.sup.-1) : 3680-3130(OH), 3300(NH), 2940, 2870(CH), 1740(ester), 1650, 1550(amido)
NMR(CDCl.sub.3) : 0.88(t,6H,JMeCH.sub.2 6.4 Hz,2MeCH.sub.2), 1.27(m,40H,20CH.sub.2), 1.37(d,3H,JMeCH7.0 Hz,MeC of Lac), 1.41[d,3H,JMeCH7.0 Hz,MeC of Ala), 1.60(m,4H,2MeCH.sub.2), 1.91(s,3H,AcN), 1.91-2.02(m,1H,CHCH.sub.2 of Gln), 2.21-2.90(m,6H,CH.sub.2 CO of Gln,2CH.sub.2 CO), 3.70(s,3H,COOMe), 4.05(t,1H,J.sub.6a,6b,10.3 Hz,H-6a), 4.22-4.26(m,2H,CH of Lac and Ala), 4.34-4.39(m,1H,CH of Gln), 5.13[d,1H,Jl.210.6 Hz,H--1), 5.21-5.25(m,1H,H--3 of C.sub.14 OC.sub.16)
EXAMPLE 20
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R)-3-hexadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanYl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 3-hexadecanoyloxytetradecanoylthio(340.0 mg, 0.350mmol) was dissolved in a mixture of dry dioxane (4.0 ml) and dry DMF(1.5 ml). To the solution were added octadecanoic acid(129.4 mg, 0.455mmol), DCC(144.4 mg, 0.700mmol) and DMAP(21.4 mg, 0.175mmol). The resultant was stirred for 3 hours at room temperature. In the same manner as that in Example 14, the title compound (203.lmg, yield : 46.8%) was obtained.
mp : 171.2.degree.-172.8.degree. C.
[.alpha.].sub.D.sup.25 :+17.01.degree. (C=0.723, CH.sub.2 Cl.sub.2 :MeOH=2 1)
IR .gamma.max(cm.sup.-1):3320, 2370(NH, OH), 2920, 2850(CH), 1740(ester), 1650, 1540(amido)
NMR(CDCl.sub.3) 0.87(t,9H,JMeCH5.3 Hz,3MeCH.sub.2), 1.25(m,70H,35CH.sub.2), 1.39(d,3H,JMeCH6.6 Hz,MeC of Ala), 1.58(m,6H,3MeCH.sub.2), 1.94(s,3H,AcN), 2.22-2.91(m,2H,CH.sub.2 CO of Gln), 2.32(t,2H,JCH.sub.2 CH.sub.2 7.7 Hz,CH.sub.2 CO of Gln), 3.69(s,3H,COOMe), 5.13(d,1H,J.sub.1.2 11.0 Hz,H--1), 5.11-5.20(m,1H,H--3 of C.sub.14 --O--C.sub.16)
EXAMPLE 21
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-octadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (III) wherein Rl is 3-octadecanoyloxytetradecanoyloxy(388.9 mg, 0.380mmol) was dissolved in 80% acetic acid aqueous solution(15 ml), which was allowed to stand for 2 hours at 45.degree. C. In the same manner as that in Example 4, the title compound (373.7 mg) was quantitatively obtained(373.7 mg).
mp : 187.degree.-188.5.degree. C.
[.alpha.].sub.D.sup.25 :+47.11.degree. (C=0.900, CH.sub.2 Cl.sub.2 :MeOH=1:1)
IR .gamma.max(cm.sup.-1) : 3700-3100(OH), 3300(NH), 2910, 2850(CH), 1740(ester), 1650, 1540(amido)
NMR(CDCl.sub.3): 0.88[t,9H,JMe.sub.1 CH.sub.2 7.0 Hz,3MeCH.sub.2), 1.25[m,44H,22CH.sub.2), 1.41(d,3H,JMeCH7.8 Hz,MeC of Ala), 1.44[d,3H,JMeCH7.8 Hz,MeC of Lac), 1.99(s,3H,AcN), 1.94-2.04(m,2H,CH.sub.2 CH of Gln), 2.30(t,2H,JCH.sub.2 CH.sub.2 8.0.sub.z,CH.sub.2 CO of Gln), 2.27-2.46(m,6H,3CH.sub.2 CO), 3.70(s,3H,COOMe), 5.30(m,1H,H--3 of C.sub.14 OC.sub.18), 6.05(d,1H,J.sub.12 7.8 Hz,H--1)
EXAMPLE 22
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-octadecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl -L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 3-octadecanoyloxytetradecanoyloxy(177,0 mg, 0.18mmol) was in a mixture of dry dioxane(3.0 ml) and dry DMF(1.0 ml). To the solution were added octadecanoic acid(66.6 mg, 0.234mmol), DCC(74.3 mg, 0.360mmol) and DMAP(11.0 mg, 0.090mmol). The resultant was stirred for 16 hours at room temperature. In the same manner as that in Example 11, the title compound (164.0 mg, 72.8%) was
mp : 106.degree.-108.5.degree. C.
[.alpha.].sub.D.sup.25 :+38.46.degree. (C=0.624, CH.sub.2 Cl.sub.2 :MeOH=1:1)
IR .gamma.max(cm.sup.-1) : 3700-3150(H), 3300(NH), 2930, 2860(CH), 1740(ester), 1660, 1540(amido)
NMR(CDCl.sub.3):0.88(t,9H,JCH.sub.2 CH.sub.2 66 Hz,3MeCH.sub.2), 1.25(m,72H,36CH.sub.2), 1.43(d,3H,JMeCH6.2 Hz,MeC of Lac), 1.59(m,6H,3MeCH.sub.2), 1.99(s,3H,AcN), 2.01-2.20(m,8H,CH.sub.2 CH of Gln,3CH.sub.2 CO), 2.30(t,2H,JCH.sub.2 CH.sub.2 7.7 Hz,CH.sub.2 CO of Gln), 3.69(s,3H,COOMe), 5.30(m,1H,H--3 of C.sub.14 OC.sub.18), 6.05(d,1H,J.sub.1.2 3.0 Hz,H--1)
EXAMPLE 23
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-octadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (III wherein R.sub.1 is 3-octadecanoyloxytetradecanoylthio(634.lmg, 0.610mmol) was dissolved in 80% acetic acid acqueous solution 15 ml , which was allowed to stand for an hour at 45.degree. C. In the same manner as that in Example 4, the title compound (609.6 mg) was quantitatively obtained.
mp : 112.5.degree.-113.8.degree. C.
[.alpha.].sub.D.sup.25 : +24.62.degree. (C=0.600, Ch.sub.2 Cl.sub.2 MeOH=1:1)
IR .gamma.max(cm.sup.-1): 3400-3100(OH), 3260(NH), 2910, 2850(CH), 1740(ester), 1640, 1530(amido)
NMR(CDCl.sub.3) 0.88(t,6H,JMeCH.sub.2,4.0 Hz,2MeCH.sub.2), 1.25(m,44H,22CH.sub.2), 1.33(d,3H,JMeCH7.3 Hz,MeC of Lac), 1.36(d,3H,JMeCH7.3 Hz,MeC of Ala), 1.58(m,4H,2MeCH.sub.2), 1.92(s,3H,AcN), 1.91-2.04(m,2H,CHCH.sub.2 of Gln), 2.26(m,6H,CH2CO of Gln,2CH.sub.2 CO), 3.69[s,3H,COOMe), 4.02-4.09(t,1H,J.sub.6a,6b 8.7 Hz,H-6a), 4.28(m,1H,CH of Gln), 5.08(d,1H,J.sub.1.2 4.0 Hz,H--1), 5.21{m,1H,H--3 of C.sub.14 --O--C.sub.18)
EXAMPLE 24
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl- 1-S-((3R)-3-octadecanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine
The compound of the formula (I') wherein R.sub.1 is 3-octadecanoyloxytetradecanoylthio(400.0 mg, 0.400mmol) was dissolved in a mixture of dry dioxane (4.0 ml) and dry DMF(1.5 ml). To the solution were added octadecanoic acid(147.9 mg, 0.520mmol , DCC(165.lmg, 0.800mmol}and DMAP(24.4 mg, 0.200mmol), and the resultant was stirred for 3.5 hours at room temperature. In the same manner as that in Example 14, the title compound (258.6 mg, yield 51.0%) was obtained.
mp : 123.1.degree.-124.5.degree. C. [.alpha.].sub.D.sup.25 :+17.01.degree. (C=0.723, CH.sub.2 Cl.sub.2 MeOH=2:1)
IR .gamma.max(cm.sup.-1) 3650-3150(OH), 3300(NH), 2930, 2850[CH), 1730(ester), 1650, 1550(amido)
NMR(CDCl.sub.3) 0.88(t,9H,JMeCH.sub.2 5.5 Hz,3MeCH.sub.2), 1.25[m,74H,37CH.sub.2), 1.34[d,3H,JMeCH6.6 Hz,MeC of Ala), 1.44-1.67(m,6H,3MeCH.sub.2), 1.85(s,3H,AcN), 2.17-2.79(m,2H,CH.sub.2 CHof Gln), 2.31(t,2H,JCHh.sub.2 CH.sub.2 8.4 Hz,CH.sub.2 CO of Gln), 3.70(s,3H,COOMe), 5.10[d,1H,J.sub.1.2 10 6 Hz,H--1), 5.14(m,1H,H--3 of C.sub.14 OC.sub.18)
EXAMPLE 25
N-[2-0-{2-Acetamido-2,3-dideoxy-1-0-((3R)-3-tetradecanoyloxytetradecanoyl}-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (III wherein R.sub.1 is 3-tetracosanoyloxytetradecanoyloxy[465.2 mg, 0.420mmol) was dissolved in 80% acetic acid aqueous solution (15 ml), which was allowed to stand for an hour at 45.degree. C. In the same manner as that in Example 4, the title compound(448.3 mg) was quantitatively obtained.
mp : 183.5.degree.-185.degree. C.
[.alpha.].sub.D.sup.25 :+34.13.degree. (C=0.920, CH.sub.2 Cl.sub.2 :MeOH=2:1)
IR.gamma.max(cm.sup.-1): 3700-3120(OH), 3300(NH), 2930, 2850(CH), 1740(ester), 1660, 1540(amido)
NMR(CDCl.sub.3) 0.89(t,9H,JMeCH.sub.2 6.6 Hz,3MeCH.sub.2), 1.25(m,56H,28CH.sub.2), 1.41(d,3H,JMeCH6.9 Hz,MeC of Ala), 1.44(d,3H,JMeCH6.9 Hz,MeC of Lac), 1.60(m,6H,3MeCH.sub.2), 1.99(s,3H,AcN), 1.94-2.01(m,2H,CH.sub.2 CHof Gln), 2.20-2.39(m,6H,3CH.sub.2 CO), 2.29(t,2H,JCH.sub.2 CH.sub.2 13 Hz,CH.sub.2 OO of Gln), 3.69(s,3H,COOMe), 5.30(m,1H,H--3 of C.sub.14 OC.sub.24), 6.05(d,1H,J.sub.1.2 2.9 Hz,H--1)
EXAMPLE 26
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-0-((3R)-3-tetradecanoyloxytetradecanoyl)-.alpha.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isogluatmine methylester
The compound of the formula (I') wherein R.sub.1 is 3-tetracosanoyloxytetradecanoyloxy (234.8 mg, 0.220 mmol) was dissolved in a mixture of dry dioxane (3.0 ml) and dry DMF(1.0 ml). To the solution were added octadecanoic acid (81.3 mg, 0.286 mmol), DCC (90.8 mg, 0.440 mmol) and DMAP(13.4 mg, 0.110 mmol), and the resultant was stirred for 12 hours at room temperature. In the same manner as that in Example 11, the title compound (200.7 mg, yield:68.3%) was obtained.
mp : 66.5.degree.-68.degree. C.
[.alpha.].sub.D.sup.25 : +34.11.degree. (c=0.680, CH.sub.2 Cl.sub.2 :MeOH=1:1)
IR .gamma.max(cm.sup.-1) : 3700-3100(OH) 3300 NH), 2930, 2850(CH), 1760(ester), 1660, 1540(amido)
NMR(CDCl.sub.3) : 0.88(t,9H,JCH.sub.2 CH.sub.2 6.6 Hz,3MeCH.sub.2), 1.25(m,88H,44CH.sub.2), 1.43(d,3H,JMeOH6.6 Hz,MeC of Ala), 1.44(d,3H,JMeOH7.0 Hz,MeC of Lac), 1.61(m,6H,3MeCH.sub.2), 2.00(m,8H,CH.sub.2 CH of Gln,3CH.sub.2 CO), 1.99(s,3H,AcN), 2.33(t,2H,JCH.sub.2 CH.sub.24 2 Hz,CH.sub.2 CO of Gln). 3.65(s,3H,COOMe), 4.20(q,1H,JMe.sub.1 CH,Hz,MeCH of Ala), 5.29(m,1H,H--3 of C.sub.14 OC.sub.24), 6.04(d,1H,J.sub.1.2 33 Hz,1-H)
EXAMPLE 27
N-[2-0-{2-Acetamido-2,3-dideoxy-1-S-((3R)-3-tetracosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (III wherein R.sub.1 is 3-tetracosanoyloxytetradecanoylthio (617.9 mg, 0.550mmol) was dissolved in 80% acetic acid aqueous solution (12 ml), which was allowed to stand for an hour at 45.degree. C. In the same manner as that in Example 4, the title compound 595.9 mg}was quantitatively obtained.
mp : 168.5.degree.-170.1.degree. C.
[.alpha.].sub.D.sup.25 :+5.18.degree. (C=0.772, CH.sub.2 Cl.sub.2 :MeOH=1:1)
IR .gamma.max(cm.sup.-1) : 3500-3200(OH), 3280(NH), 2910, 2850(CH), 1720(ester), 1630, 1540(amido)
NMR(CDCl.sub.3) 0.88(t,6H,JMe.sub.1 CH.sub.2 Hz,2MeCH.sub.2) 1.25(m,56H,28CH.sub.2), 1.30(d,3H,JMeCH8.3 Hz,MeC of Lac), 1.34(d,3H,JMeCH7.5 Hz,MeC of Ala), 1.58(m,4H,2MeCH.sub.2), 1.97-1.91(m,2H,2MeCH.sub.2), 1.94(s,3H,AcN), 2.25(m,6H,CHCH.sub.2 of Gln), 3.69(s,3H,COOMe), 4.05(t,1H,J.sub.6a,6b 10.1 Hz,H--6a), 4.24-4.28(m,1H,CH of Gln), 5.09(d,1H,J.sub.1.2 10.8 Hz,H--1), 5.13-5.19(m,1H,H--3 of C.sub.14 --O--C.sub.24)
EXAMPLE 28
N-[2-0-{2-Acetamido-2,3-dideoxy-6-0-octadecanoyl-1-S-((3R}-3-tetracosanoyloxytetradecanoyl)-1-thio-.beta.-D-glucopyranos-3-Yl}-D-lactoyl]-L-alanyl-D-isoglutamine methylester
The compound of the formula (I') wherein R.sub.1 is 3-tetracosanoyloxytetradecanoylthio (411.8 mg, 0.380mmol) was dissolved in a mixture of dry dioxane 4.0 ml) and dry DMF (1.5 ml). To the solution were added octadeconoic acid (140.5 mg, 0.494mmol), DCC(156.8 mg, 0.760mmol) and DMAP (23.2 mg, 0.190mmol), and the resultant was stirred for 3 hours at room temperature. In the same manner as that in Example 14, the title compound (223.5 mg, yield:43.5%) was obtained.
mp : 147.5.degree.-149.0.degree. C.
[.alpha.].sub.D.sup.25 :+17.40.degree. (C=0.632,CH.sub.2 Cl.sub.2 :MeOH=1:1)
IR .gamma.max(cm.sup.-1): 3600-32 00(OH), 3300{NH), 2950, 2880(CH), 1750(ester), 1660, 1560(amido)
NMR(CDCl.sub.3) 0.88(t,9H,JMeCH5.5 Hz,3MeCH.sub.2), 1.25(m,86H,43CH.sub.2), 1.35(d,3H,JMeCH6.3 Hz,MeC of Ala), 1.57(m,6H,3MeCH.sub.2), 1.90(s,3H,AcN), 2.05-2.90(m,2H,CH.sub.2 CH of Gln), 2.35(t,2H,JCH.sub.2 CH.sub.2 7.8 Hz,CH.sub.2 CO of Gln), 3.68(s,3H,COOMe), 5.13{d,1H,J.sub.1.2 11.0 Hz,H--1), 5.15(m,1H,H--3 of C.sub.14 OC.sub.24)
Pharmacological activities of the compounds of the present invention are shown as follows.
(1) Hepatitis-vaccine enhancing activity (adjuvant activity)
A compound of the present invention was dissolved in lipidmicrosphere (1 mg/ml). On the other hand, a solution of hepatitis B virus surface antigen (HBs) in physiological saline was prepared (50 .mu.g/ml). The above solutions in equal amounts were mixed to prepare a test solution. A control solution was prepared by the exclusion of the compound of the present invention from said test solution. A mixture of a suspension of aluminium hydroxide gel in physiological saline (1 mg/ml) and said hepatitis vaccine preparation in equal amounts was prepared as another control solution. The test solution (0.2 ml) was intraperitoneally administered to each mouse in one group consisting of seven female CDF.sub.1 mice.
Blood samples were collected from the fundus ocluli vein of each mouse every week after the administration and then centrifuged to obtain serums. Three weeks after the administration, 0.2 ml of the test liquid was intraperitoneally administered again to each mouse for secondary stimulation. Then blood collecting was conducted every week to obtain serums after the application of the secondary stimulation, in the same manner as that described above.
The amount of the IgG antibodies against the hepatitis B virus surface antigens (HBs) in the serums thus obtained was determined with an ELISA method. The results are shown in Table 1.
TABLE 1__________________________________________________________________________Testmaterial 1 W 2 W 3 W 4 W 5 W__________________________________________________________________________ **Adjuvant activities on heptatis Bvirus surface antigens - Experiment 1 Anti HBs serum antigen value (average value .+-. S.D.) O.D 415 nm 5000-fold dilutionExample 1 0.001 .+-. 0.001 0.018 .+-. 0.000 0.074 .+-. 0.002 0.815 .+-. 0.011 0.843 .+-. 0.005 2 0 0.023 .+-. 0.000 0.076 .+-. 0.001 0.975 .+-. 0.008 0.930 .+-. 0.004 3 0 0.027 .+-. 0.001 0.064 .+-. 0.003 0.631 .+-. 0.006 0.692 .+-. 0.009 4 0 0.073 .+-. 0.001 0.111 .+-. 0.007 0.848 .+-. 0.009 0.935 .+-. 0.022 5 0.001 .+-. 0.001 0.021 .+-. 0.001 0.048 .+-. 0.001 0.643 .+-. 0.013 0.490 .+-. 0.009 6 0 0.020 .+-. 0.002 0.069 .+-. 0.001 0.477 .+-. 0.005 0.529 .+-. 0.005 7 0 0.016 .+-. 0.003 0.071 .+-. 0.004 0.426 .+-. 0.000 0.470 .+-. 0.010 8 0 0.067 .+-. 0.003 0.114 .+-. 0.002 0.897 .+-. 0.012 0.845 .+-. 0.016 9 0.014 .+-. 0.002 0.092 .+-. 0.003 0.149 .+-. 0.001 0.681 .+-. 0.012 0.702 .+-. 0.006 10 0 0.061 .+-. 0.002 0.114 .+-. 0.003 0.778 .+-. 0.024 0.878 .+-. 0.009 11 0.010 .+-. 0.002 0.083 .+-. 0.002 0.124 .+-. 0.003 0.602 .+-. 0.009 0.716 .+-. 0.020 12 0.007 .+-. 0.003 0.109 .+-. 0.002 0.111 .+-. 0.001 0.608 .+-. 0.021 0.695 .+-. 0.021 13 0 0.081 .+-. 0.003 0.126 .+-. 0.003 0.635 .+-. 0.011 0.742 .+-. 0.016 14 0 0.071 .+-. 0.000 0.104 .+-. 0.003 0.784 .+-. 0.022 0.846 .+-. 0.024 15 0 0.085 .+-. 0.002 0.129 .+-. 0.001 0.788 .+-. 0.008 0.905 .+-. 0.020 16 0 0.079 .+-. 0.004 0.103 .+-. 0.004 0.850 .+-. 0.008 0.903 .+-. 0.021Aluminum 0 0 0 0.027 .+-. 0.001 0.040 .+-. 0.001hydroxidegelControl 0 0 0 0.097 .+-. 0.006 0.123 .+-. 0.001 **Adjuvant activities on heptatis Bvirus surface antigens - Experiment 2 Anti HBs serum antigen value (average value .+-. S.D.) O.D 415 nm 2000-fold dilutionExample 17 0.001 .+-. 0.004 0.026 .+-. 0.001 0.051 .+-. 0.001 0.642 .+-. 0.021 0.615 .+-. 0.021 18 0 0.035 .+-. 0.007 0.050 .+-. 0.004 0.481 .+-. 0.006 0.375 .+-. 0.008 19 0 0.023 .+-. 0.000 0.042 .+-. 0.001 0.536 .+-. 0.011 0.521 .+-. 0.012 20 0.002 .+-. 0.001 0.044 .+-. 0.005 0.056 .+-. 0.003 0.814 .+-. 0.018 0.708 .+-. 0.002 21 0.006 .+-. 0.004 0.038 .+-. 0.000 0.058 .+-. 0.007 0.517 .+-. 0.006 0.498 .+-. 0.011 22 0.005 .+-. 0.004 0.036 .+-. 0.007 0.053 .+-. 0.001 0.294 .+-. 0.006 0.254 .+-. 0.002 23 0.004 .+-. 0.001 0.051 .+-. 0.003 0.092 .+-. 0.004 0.639 .+-. 0.003 0.626 .+-. 0.008 24 0.007 .+-. 0.001 0.034 .+-. 0.001 0.050 .+-. 0.000 0.579 .+-. 0.007 0.513 .+-. 0.011 25 0.004 .+-. 0.002 0.021 .+-. 0.001 0.031 .+-. 0.004 0.402 .+-. 0.011 0.434 .+-. 0.021 26 0.001 .+-. 0.006 0.015 .+-. 0.006 0.032 .+-. 0.008 0.192 .+-. 0.002 0.163 .+-. 0.004 27 0.003 .+-. 0.003 0.031 .+-. 0.002 0.052 .+-. 0.000 0.580 .+-. 0.016 0.573 .+-. 0.013 28 0.005 .+-. 0.003 0.062 .+-. 0.004 0.086 .+-. 0.004 0.611 .+-. 0.018 0.543 .+-. 0.029Aluminum 0 0.002 .+-. 0.002 0.006 .+-. 0.004 0.196 .+-. 0.003 0.227 .+-. 0.001hydroxidegelControl 0 0.017 .+-. 0.000 0.022 .+-. 0.001 0.267 .+-. 0.004 0.232 .+-. 0.004__________________________________________________________________________
(2) Influenza HA vaccine enhancing activity (adjuvant activity)
A compound of the present invention was dissolved in lipidmicrosphere (lmg/ml). On the other hand, a solution of influenza HA vaccine (B/nagasaki/1/87 strain) in physiological saline was prepared (100 ccA/ml). The above solutions in equal amounts were mixed to prepare a test solution. A control solution was made by the exclusion of the compound of the present invention from said test liquid. A mixture of a suspension of aluminium hydroxide gel in physiological saline(lmg/ml) and said influenza HA vaccine preparation in equal amounts was prepared as another control liquid. The test solution (0.2 ml) was intraperitoneally administered to each mouse in one group consisting of seven female CDF.sub.1 mice.
Blood samples were collected from the fundus oculi vein of each mouse every week after the administration and then centrifuged to obtain serums. Three weeks after the aministration, 0.2 ml of the test liquid was intraperitoneally administered again to each mouse for secondary stimulation. Then, blood collecting was conducted every week to obtain serums after the application of the secondary stimulation, in the same manner as that described above.
The amount of the IgG antibodies against the influenza HA vaccine (B/Nagasaki/1/87 strain) in the serums thus obtained was determined with an ELISA method. The results are shown in Table 2.
TABLE 2__________________________________________________________________________Testmaterial 1 W 2 W 3 W 4 W 5 W__________________________________________________________________________ **Adjuvant activities on influenza HAvaccines - Experiment 1 Anti HA serum antigen value (average value .+-. S.D.) O.D 415 nm 5000-fold dilutionExample 1 0.007 .+-. 0.003 0.174 .+-. 0.003 0.232 .+-. 0.003 1.243 .+-. 0.036 1.201 .+-. 0.002 2 0.003 .+-. 0.001 0.172 .+-. 0.004 0.420 .+-. 0.005 0.447 .+-. 0.029 1.418 .+-. 0.035 3 0.009 .+-. 0.000 0.182 .+-. 0.003 0.292 .+-. 0.004 0.122 .+-. 0.020 1.140 .+-. 0.013 4 0.004 .+-. 0.001 0.215 .+-. 0.001 0.381 .+-. 0.004 1.204 .+-. 0.012 1.150 .+-. 0.016 5 0 0.091 .+-. 0.002 0.377 .+-. 0.001 1.037 .+-. 0.027 1.068 .+-. 0.004 6 0.001 .+-. 0.001 0.013 .+-. 0.002 0.259 .+-. 0.004 1.025 .+-. 0.013 1.159 .+-. 0.013 7 0.001 .+-. 0.001 0.112 .+-. 0.003 0.286 .+-. 0.001 1.039 .+-. 0.010 1.128 .+-. 0.026 8 0.001 .+-. 0.001 0.105 .+-. 0.005 0.246 .+-. 0.004 1.246 .+-. 0.019 1.267 .+-. 0.023 9 0.019 .+-. 0.002 0.168 .+-. 0.005 0.392 .+-. 0.006 1.342 .+-. 0.005 1.329 .+-. 0.026 10 0.005 .+-. 0.001 0.153 .+-. 0.003 0.280 .+-. 0.000 1.149 .+-. 0.018 1.203 .+-. 0.014 11 0 0.073 .+-. 0.000 0.160 .+-. 0.005 1.059 .+-. 0.016 1.050 .+-. 0.003 12 0 0.105 .+-. 0.004 0.176 .+-. 0.002 1.039 .+-. 0.015 1.050 .+-. 0.008 13 0 0.088 .+-. 0.004 0.140 .+-. 0.001 0.868 .+-. 0.010 0.824 .+-. 0.002 14 0 0.110 .+-. 0.003 0.186 .+-. 0.007 0.974 .+-. 0.006 0.954 .+-. 0.002 15 0.007 .+-. 0.000 0.119 .+-. 0.005 0.218 .+-. 0.006 1.249 .+-. 0.013 1.262 .+-. 0.017 16 0.001 .+-. 0.001 0.145 .+-. 0.004 0.257 .+-. 0.010 1.251 .+-. 0.010 1.262 .+-. 0.026Aluminum 0 0 0 0.162 .+-. 0.004 1.263 .+-. 0.007hydroxidegelControl 0 0 0 0.410 .+-. 0.004 0.502 .+-. 0.008 *Adjuvant activities on influenza HAvaccines - Experiment 2 Anti HA serum antigen value (average value .+-. S.D.) O.D 415 nm 8000-fold dilutionExample 17 0.010 .+-. 0.002 0.122 .+-. 0.006 0.191 .+-. 0.001 0.611 .+-. 0.017 0.696 .+-. 0.014 18 0 0.052 .+-. 0.004 0.075 .+-. 0.001 0.370 .+-. 0.005 0.360 .+-. 0.001 19 0 0.125 .+-. 0.003 0.187 .+-. 0.001 0.872 .+-. 0.002 0.936 .+-. 0.006 20 0.001 .+-. 0.001 0.071 .+-. 0.001 0.110 .+-. 0.008 0.840 .+-. 0.011 0.857 .+-. 0.023 21 0 0.060 .+-. 0.001 0.097 .+-. 0.002 0.748 .+-. 0.003 0.758 .+-. 0.012 22 0.001 .+-. 0.004 0.065 .+-. 0.001 0.100 .+-. 0.003 0.411 .+-. 0.009 0.492 .+-. 0.002 23 0.008 .+-. 0.005 0.096 .+-. 0.001 0.183 .+-. 0.004 0.949 .+-. 0.006 1.030 .+-. 0.003 24 0.006 .+-. 0.001 0.085 .+-. 0.005 0.113 .+-. 0.007 0.771 .+-. 0.003 0.791 .+-. 0.004 25 0.009 .+-. 0.001 0.109 .+-. 0.002 0.149 .+-. 0.004 0.623 .+-. 0.019 0.719 .+-. 0.021 26 0.004 .+-. 0.003 0.038 .+-. 0.001 0.054 .+-. 0.001 0.208 .+-. 0.001 0.206 .+-. 0.002 27 0 0.110 .+-. 0.003 0.161 .+-. 0.003 0.751 .+-. 0.004 0.805 .+-. 0.008 28 0.008 .+-. 0.004 0.041 .+-. 0.004 0.061 .+-. 0.001 0.787 .+-. 0.018 0.779 .+-. 0.024Aluminum 0 0 0 0.152 .+-. 0.008 0.181 .+-. 0.008hydroxidegelControl 0 0.046 .+-. 0.001 0.071 .+-. 0.004 0.380 .+-. 0.004 0.388 .+-. 0.005__________________________________________________________________________
(3) Activation of macrophages (an effect which inhibits the growth of tumor cells)
A compound of the present invention was dissolved in lipidmicrosphere to obtain a solution in a concentration of 500.mu.g/ml, and 0.2 ml of such solution was intraperitoneally administered to each mouse in one group consisting of seven female CDF.sub.1 mice. Intraperitoneal macrophages obtained three days after the administration and L-1210 mouse leukemia cells were mixed in the ratio of cell numbers of 20:1, respectively. Two hundred .mu.l of the mixture was placed in each well of one sheet of 96 well microtiter plate. After 72 hours, the increase of the cell number in each well was determined by a MTT assay method. The ratio of the cell number for the mixture of the L-1210 cells and the macrophage relative to the cell number for the L-1210 cells only(growth inhibitory ratio) was determined, and the results are shown in Table 3.
TABLE 3______________________________________Test Growth inhibitory ratio ofmaterial L-1210 mouse leukemia cells (%)______________________________________Example 1 40.02 41.33 42.64 45.25 57.86 63.07 90.28 57.99 58.510 76.611 59.712 79.013 39.714 96.415 87.516 76.3Control 9.1______________________________________

Muramyl peptide derivatives and immunoregulating compositions containing them

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Japanese Published Unexamined Patent Appln. No. 172399/1983.
Japanese Published Unexamined Patent Appln. No. 20297/1984.
Japanese Published Unexamined Patent Appln. No. 275299/1986.
Saishin Igaku, 43, No. 6, pp. 1268-1276 (1988).
Kusumoto et al., Tetrahedion Letters, No. 49, "Synthesis of Long Chain Fatty Acid Esters of N-Acetylmuramyl-L-Alanyl-D-Isoglutamine in Relation to Antitumor Activity", pp. 4899-4902 (1978).
K. Matsumoto et al., Immunostimulants Now and Tomorrow, pp. 79-97 (1987).