Claims
- 1. A process for preparing an aminopropylaminobleomycin derivative having the formula
- [BX]--NH--(CH.sub.2).sub.3 --A--(CH.sub.2).sub.3 --B
- wherein
- [BX] represents the bleomycin acid acyl group: ##STR13## R.sub.1 and R.sub.2 are independently lower alkyl or benzyl; R is lower alkylene;
- n is the integer 0 or 1; and
- B has the formula ##STR14## wherein (i) R.sub.3 is hydrogen and R.sub.4 is
- (a) benzyl substituted by one or more halogen atoms, provided that the benzyl is substituted by two halogen atoms when R.sub.1 is lower alkyl,
- (b) benzyl substituted by cyano, two or more alkoxy groups or two or more benzyloxy groups,
- (c) lower alkyl substituted by cycloalkyl or anthranyl,
- (d) phenylethyl substituted by one or more halogen atoms, or
- (e) diphenylethyl; or
- (ii) both R.sub.3 and R.sub.4 are benzyl which may be substituted by one or more
- (a) benzyloxy groups,
- (b) ring substituted benzyloxy groups in which the ring substituents may be one or more halogen atoms, lower alkoxy groups or benzyloxy groups, or
- (c) cycloalkylmethoxy groups;
- which comprises allowing an aminopropylaminobleomycin represented by the general formula
- [BX]--NH--(CH.sub.2).sub.3 --A--(CH.sub.2).sub.3 --NH.sub.2
- wherein
- [BX] and A are as defined above, to condense reductively with a carbonyl compound represented by the general formula
- R.sub.5 --CO--R.sub.6
- wherein
- R.sub.5 and R.sub.6 are independently (1) a hydrogen atom, (2) a cycloalkyl, (3) an alkyl which may be substituted by one or more cycloalkyl or phenyl groups (the phenyl group may be substituted by a halogen atom, (4) phenyl which may be substituted by one or more halogen atoms or lower alkyl, cycloalkylmethyloxy, lower alkoxy, benzyloxy, cyano, halomethyl, halobenzyloxy, (lower)-alkoxybenzyloxy, or benzyloxybenzyloxy groups, (5) anthranyl; provided that at least either one of R.sub.5 and R.sub.6 is a group other than hydrogen atom.
- 2. A process according to claim 1, wherein ##STR15## wherein R.sub.1 is a lower alkyl,
- R.sub.2 is a lower alkyl or benzyl,
- n is the integer 0 or 1; and
- R.sub.5 and R.sub.6 are each (1) a hydrogen atom, (2) a cycloalkyl, (3) an alkyl substituted by a halogenophenyl, (4) phenyl which may be substituted by one or more halogen atoms or benzyloxy, cyano, halomethyl, halobenzyloxy, lower-alkoxybenzyloxy, benzyloxybenzyloxy, or cycloalkylmethyloxy groups, (5) anthranyl; provided that at least either one of R.sub.5 and R.sub.6 is a group other than hydrogen atom.
- 3. A process according to claim 1, wherein ##STR16## R.sub.5 is a hydrogen atom, and R.sub.6 is a phenyl group which may be substituted by one or more benzyloxy, or cycloalkyl groups.
- 4. A process according to claim 1, wherein ##STR17## and
- R.sub.5 --CO--R.sub.6 is cycloundecanecarbaldehyde or benzaldehyde, the latter of which may be substituted by one or more benzyloxy groups.
- 5. A process to claim 1, wherein
- the molar ratio of the aminopropylaminobleomycin to the carbonyl compound is 1:0.5-25.
- 6. A process according to claim 1, wherein
- the condensation is carried out in a solvent and in the presence of a reducing agent at -5.degree. to 70.degree. C. for 3 to 70 hours.
- 7. A process according to claim 6, wherein
- the solvent is methanol, water, dimethylformamide, acetonitrile, or a mixture thereof.
- 8. A process according to claim 6, wherein
- the reducing agent is a boron hydride compound or palladium-carbon.
Priority Claims (1)
Number |
Date |
Country |
Kind |
56-210449 |
Dec 1981 |
JPX |
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CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation of our copending application Ser. No. 635,096 filed July 27, 1984 now U.S. Pat. No. 4,537,880 which is a continuation-in-part or our copending application Ser. No. 453,254 filed Dec. 27, 1982, and now abandoned.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
RE30451 |
Umezawa et al. |
Dec 1980 |
|
3922262 |
Umezawa et al. |
Nov 1975 |
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3929993 |
Takita et al. |
Dec 1975 |
|
Non-Patent Literature Citations (2)
Entry |
J. of Antibiotics, Umezawa, Maeda, et al., 19A, pp. 200-209 (1966). |
J. of Antibiotics, Umezawa, Suhara, et al., 19A, pp. 210-215 (1966). |
Continuations (1)
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Number |
Date |
Country |
Parent |
635096 |
Jul 1984 |
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
453254 |
Dec 1982 |
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