Claims
- 1. A process for the resolution of an amino acid of the formula III.sub.1 ##STR19## wherein Z is the organic remainder of an amino acid having a total of at most 9 carbon atoms, B is the remainder of a heterocyclic amino acid of the formula ##STR20## having a total of 3 to 6 carbon atoms, said process consisting essentially of reacting a well defined optical isomer of a compound of the formula ##STR21## wherein A is a hydrocarbon chain of 1 to 10 chain members optionally having a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur and optionally one or more unsaturations and the chain members being a mono- or polycyclic system or is a system of spiro or endo type and may have one or more chiral atoms with an ester of an amino acid of formula III.sub.A ##STR22## or with an ester of a cyclic amino acid of formula III.sub.B ##STR23## wherein Z and B have the above definitions and Y is a substituent derived from a primary, secondary or tertiary alcohol of the formula YOH, to obtain the corresponding compound of formula I ##STR24## wherein A has the above definition and R is selected from the group consisting of ##STR25## wherein Y, Z and B have the above definitions, said compound of formula I being a mixture of diastereoisomers, the lactone moiety being a well defined optical isomer and the chiral center or centers of the ester of the amino acid moiety not having an unequivocal configuration, then separating by crystallization or chromatography, the diastereo isomeric compounds contained in the mixture then subjecting the individual isomers to acid hydrolysis to obtain an ester of the amino acid of the above formula and reacting the latter with a hydrolysis agent to obtain the corresponding amino acid with an asymmetrical carbon of unequivocal configuration.
- 2. The process of claim 1 wherein the lactone is selected from the group consisting of (3R,3aR,4S,7R,7aS) 3-hydroxy-tetrahydro-4,7-methano-isobenzofuran-1-one and (3S, 3aS,4R,7S,7aR) 3-hydroxy-tetrahydro-4,7-methano-isobenzofuran1-one.
- 3. The process of claim 1 wherein the ester of the amino acid is selected from the group consisting of benzyl leucinate, benzyl prolinate, methyl phenylalaninate and methyl methioninate.
- 4. The method of claim 1 wherein the water of reaction formed by the reaction of the lactone and the ester is eliminated.
- 5. The method of claim 4 wherein the water of reaction is removed by azeotropic distillation with a solvent selected from the group consisting of chlorinated solvents, aromatic hydrocarbons, aliphatic hydrocarbons and ethers and the distillation is optionally effected under reduced pressure.
Priority Claims (1)
Number |
Date |
Country |
Kind |
79 30201 |
Dec 1979 |
FRX |
|
PRIOR APPLICATION
This application is a continuation of U.S. patent application Ser. No. 690,474 filed Jan. 10, 1985, now abandoned which is a division of our copending patent application Ser. No. 393,812 filed Jun. 30, 1982, now U.S. Pat. No. 4,513,139 which is a division of U.S. patent application Ser. No. 212,569 filed Dec. 30, 1980, now U.S. Pat. No. 4,350,687.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
2904554 |
Wheeler et al. |
Sep 1959 |
|
4224239 |
Tashiro et al. |
Sep 1980 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
4493 |
Oct 1979 |
EPX |
2510714 |
Sep 1979 |
DEX |
Divisions (2)
|
Number |
Date |
Country |
Parent |
393812 |
Jun 1982 |
|
Parent |
212569 |
Dec 1980 |
|
Continuations (1)
|
Number |
Date |
Country |
Parent |
690474 |
Jan 1985 |
|