US4008218A
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1-N-((S)-α-substituted-ω-aminoacyl)-neamine or -ribostamycin and the production thereof
Assignee: Meiji Seika Kaisha Ltd
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Filing: 1975-03-19
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Granted: 1977-02-15
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Expires: 1995-03-19
Abstract
Abstract An 1-N-((S)-α-substituted-ω-aminoacyl)-neamine or -ribostamycin of the formula: ##STR1## wherein R is a hydrogen atom or β-D-ribofuranosyl group of the formula ##STR2## and R 3 is hydroxyl, amino-NH 2 or acylamino group --NHR 4 in which R 4 is an acyl group, and n is a whole number of 1 to 4, may be produced by subjecting the corresponding O-((S)-α-substituted-ω-aminoacyl)-neamine or -ribostamycin of the formula ##STR3## or its hydroxyl-masked and amino-masked form, to the action of a basic medium to produce an acyl-migration product of the formula: ##STR4## and, optionally converting the amino-masking groups into hydrogen atoms and also the hydroxyl-masking group into hydrogen atom in a known manner if said amino-masking groups and said hydroxyl-masking groups are present in the acyl-migration product. The 1-N-((S)-α-substituted-ω-aminoacyl)-neamine or -ribostamycin produced is characterized by its useful activity inhibitory to the growth of bacteria resistant to the parent substance neamine or ribostamycin.
Inventors
- 👤 Eiichi Akita
- 👤 Tsutomu Tsuchiya
- 👤 Shinichi Kondo
- 👤 Shuntaro Yasuda
- 👤 Sumio Umezawa
- 👤 Hamao Umezawa
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 21:32
CPC Classifications
C; C07; C07H; C07H15/00; C07H15/20; C07H15/22; C07H15/222; C07H15/224; C07H15/226; C07H15/228; C07H15/23
Claims Analysis
Total Claims: 3
Claim 1
Independent Claim
214 words
A process for the production of a 1-N-((S)-α-substituted-ω-aminoalkanoyl-neamine or -ribostamycin of the formula: ##STR26## wherein R is a hydrogen atom or β-D-ribofuranosyl group of the formula: ##STR27## and R 3 is hydroxyl, amino or acetylamino and n is a whole number of 1 to 4, which consists essentially of the following four steps: a. reacting neamine or ribostamycin with trifluoroacetic acid in an organic solvent to prepare neamine tetra-trifluoroacetate or ribostamycin tetra-trifluoroacetate; b. esterifying at random the hydroxyl groups of the neamine tetra-trifluoroacetate or ribostamycin tetra-trifluoroacetate by reacting with an (S)-α-substituted-ω-phthalimidoalkanoic acid of the formula: R.sub.1 'R.sub.2 'N--(CH.sub.2).sub.n -- CH(R.sub.3)--COOH wherein R 1 ' and R 2 ' taken together form a phthaloyl group, R 3 is hydroxyl, amino, phthalimido or acetylamino, and n is a whole number of 1 to 4, to prepare a mixture of differently O-(S)-α-substituted-ω-phthalimidoalkanoylated neamine tetra-trifluoroacetates or ribostamycin tetra-trifluoroacetate; c. treating the whole mixture of said differently O-(S)-α-substituted-ω-phthalimidoalkanoylated products with aqueous hydrazine or a basic anion-exchange resin, to effect the liberation of the trifluoroacetic acid, the removal of the phthaloyl group and the migration of the (S)-α-substituted-ω-aminoalkanoyl group from the 6-hydroxyl group to the 1-amino group of the neamine or ribostamycin moiety simultaneously, whereby the desired 1-N-((S)-α-substituted-ω-aminoalkanoyl)-neamine or -ribostamycin is formed, and d. recovering said desired 1-N-((S)-α-substituted-ω-aminoalkanoyl)-neamine or -ribostamycin.
Claim 2
Dependent Claim
214 words
A process for the production of a 1-N-((S)-α-substituted-ω-aminoalkanoyl-neamine or -ribostamycin of the formula: ##STR26## wherein R is a hydrogen atom or β-D-ribofuranosyl group of the formula: ##STR27## and R 3 is hydroxyl, amino or acetylamino and n is a whole number of 1 to 4, which consists essentially of the following four steps: a. reacting neamine or ribostamycin with trifluoroacetic acid in an organic solvent to prepare neamine tetra-trifluoroacetate or ribostamycin tetra-trifluoroacetate; b. esterifying at random the hydroxyl groups of the neamine tetra-trifluoroacetate or ribostamycin tetra-trifluoroacetate by reacting with an (S)-α-substituted-ω-phthalimidoalkanoic acid of the formula: R.sub.1 'R.sub.2 'N--(CH.sub.2).sub.n -- CH(R.sub.3)--COOH wherein R 1 ' and R 2 ' taken together form a phthaloyl group, R 3 is hydroxyl, amino, phthalimido or acetylamino, and n is a whole number of 1 to 4, to prepare a mixture of differently O-(S)-α-substituted-ω-phthalimidoalkanoylated neamine tetra-trifluoroacetates or ribostamycin tetra-trifluoroacetate; c. treating the whole mixture of said differently O-(S)-α-substituted-ω-phthalimidoalkanoylated products with aqueous hydrazine or a basic anion-exchange resin, to effect the liberation of the trifluoroacetic acid, the removal of the phthaloyl group and the migration of the (S)-α-substituted-ω-aminoalkanoyl group from the 6-hydroxyl group to the 1-amino group of the neamine or ribostamycin moiety simultaneously, whereby the desired 1-N-((S)-α-substituted-ω-aminoalkanoyl)-neamine or -ribostamycin is formed, and d. recovering said desired 1-N-((S)-α-substituted-ω-aminoalkanoyl)-neamine or -ribostamycin.
Claim 3
Dependent Claim
54 words
A process as claimed in claim 1 in which the step (b) of treating the mixture of the differently O-alkanoylated products is carried out with aqueous hydrazine at a temperature of 50°-100° C in solution in an alkanol of 1-4 carbon atoms using the hydrazine in an amount sufficient to make the solution basic.
References Cited (Backward Citations)
US3792037A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-02-15 | 1980-08-16 | 1981-02-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-02-15 | 1984-08-16 | 1985-02-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-02-15 | 1988-08-16 | 1989-02-15 | $7700.00 | Window Closed / Lapsed |