US 4,357,466 A · Processes for the production of 3'-deoxykanamycin A and intermediates

Abstract

3'-Deoxykanamycin A useful as antibacterial agent is produced from a protected kanamycin A derivative either by a process comprising imidazolylthiocarbonylation of the 3'- and 2"-hydroxyl groups of 4",6"-O-cyclohexylidene-4'-0:6'-N-carbonyl-5,2'-O-isopropylidene-1,3,3"-tr i-N-tosylkanamycin A, preferential removal of the 3'-imidazolylthiocarbonyloxy group with tributyltin hydride for the 3'-deoxygenation, followed by removal of the 2"-O-imidazolylthiocarbonyl group with aqueous ammonia, removal of the N-tosyl groups with alkali or alkaline earth metal in liquid ammonia, hydrolytic fission of the 4',6'-cyclic carbamate ring and concurrent removal of the 5,2'-O-isopropylidene group and 4",6"-O-cyclohexylidene group, or by a process comprising selective acetylation of the 2"-hydroxyl group of said protected kanamycin A derivative with acetyl chloride in pyridine, trifluoromethanesulfonylation of the 3'-hydroxyl group, followed by concurrent removal of the 3'-trifluoromethanesulfonyloxy group and N-tosyl groups with alkali metal in liquid ammonia, removal of the 2"-O-acetyl group concurrently with hydrolytic fission of 4',6'-cyclic carbamate, and hydrolytic removal of the 5,2'-O-isopropylidene and 4",6"-O-cyclohexylidene groups.

Claims5

Dependent claims

A process for the production of 3'-deoxykanamycin A, which comprises the steps of:

(a) reacting a protected kanamycin A derivative of the formula ##STR12## wherein Ts denotes a tosyl group, with at least 2 molar proportions of thiocarbonyl di-imidazole in an organic solvent at a temperature of 40.degree.-150.degree. C. to effect the introduction of the imidazolylthiocarbonyl groups into the 3' and 2"-hydroxyl groups of the protected kanamycin A derivative (I), giving the corresponding, bis-imidazolylthiocarbonylated product,
(b) removing the 3'-imidazolyl-thiocarbonyloxy group from the bis-imidazolylthiocarbonylated product by reacting with tri-butyltin hydride in an organic solvent at a temperature of 40.degree.-150.degree. C. to produce the 3'-deoxygenated product of the formula ##STR13## wherein Ts is as defined above, (c) removing the 2"-O-imidazolylthiocarbonyl group from the above 3'-deoxygenated product by reacting with aqueous ammonia,
(d) removing the N-tosyl groups by reacting with an alkali metal or alkaline earth metal in liquid ammonia,
(e) opening the 4',6'-cyclic carbamate ring by basic hydrolysis, and
(f) removing concurrently the 5,2'-O-isopropylidene group and the 4",6"-O-cyclohexylidene group by acidic hydrolysis, to produce the desired 3'-deoxykanamycin A.

2 more elements

Dependencies are inferred from the claim text.

Processes for the production of 3'-deoxykanamycin A and intermediates

Life of this patent

Processes for the production of 3'-deoxykanamycin A and intermediates

Life of this patent

Abstract

Claims5