Process for the production of 3'-deoxykanamycin A and intermediate product

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

• reacting a tetra-N-protected, 4",6"-O-protected kanamycin A derivative of the formula (IV) ##STR19## wherein R represents an alkyl, aralkyl or aryl group, and Y represents an alkylidene or arylidene group of the formula ##STR20## where P and P' are each a hydrogen atom, an alkyl or aryl group, or Y is a cycloalkylidene or tetrahydropyranilidene group, with an alkanoic acid chloride having 2-4 carbon atoms or benzoyl chloride in pyridine below 5.degree. C. to form the 2',3',2"-tri-O-acylated derivative of the formula (II) ##STR21## wherein R and Y are as defined above and X is the alkanoyl group having 2-4 carbon atoms or benzoyl group,
• reacting the compound of the formula (II) with 3',4'-dihydro-2H-pyran or 5,6-dihydro-4-methoxy-2H-pyran in a solvent in the presence of a catalytic amount of p-toluenesulfonic acid at 15.degree.-25.degree. C. to form the 4'-O-pyranylated derivative of the formula (V) ##STR22## wherein R, X and Y are as defined above and Z represents a pyranyl group, reacting the 4'-O-pyranylated compound of the formula (V) in solution in a (C.sub.1 -C.sub.4) alkanol with sodium or potassium methoxide or ethoxide at 15.degree.-25.degree. C. to remove the 2'-, 3'- and 2"-acyl group (X) therefrom, giving the partially deprotected compound of the formula (VI) ##STR23## wherein R, Y and Z are as defined above, reacting the deprotected compound of the formula (VI) with an alkanoyl chloride of 2-4 carbon atoms or benzoyl chloride at a temperature lower than room temperature to selectively acylate the 2'- and 2"-hydroxyl groups, giving the 3'-O-unprotected, 2',2"-di-O-acyl derivative of the formula (VII) ##STR24## wherein R, Y and Z are as defined above and X represents the alkanoyl of 2-4 carbon atoms or benzoyl group,
• reacting the compound of the formula (VII) with mesyl chloride, tosyl chloride or benzylsulfonyl chloride in pyridine at 50.degree.-80.degree. C. to form the 3'-O-sulfonylated derivative of the formula (VIII) ##STR25## wherein R, X and Z are as defined above and W represents a mesyl, tosyl or benzylsulfonyl group,
• reacting the compound of the formula (VIII) with acetic acid, trifluoroacetic acid or hydrochloric acid in a (C.sub.1 -C.sub.4) alkanol at 20.degree.-50.degree. C. to remove the 4'-hydroxyl-protecting group (Z) and the 4",6"-O-hydroxyl-protecting group (Y) therefrom, giving the 2',2"-di-O-acyl-3'-O-sulfonyl-tetra-N-protected kanamycin A derivative of the formula (I) ##STR26## wherein R, X and W are as defined above, reacting the protected kanamycin A derivative of the formula (I) with an alkali metal alcoholate in a (C.sub.1 -C.sub.4) alkanol at 15.degree.-30.degree. C. to effect 2',3'- and 3',4'-epoxidations and simultaneously removal of the 2'- and 2"-acyl groups (X) therefrom,
• reducing the resultant anhydro derivatives as formed in solution in said alkanol with hydrogen in the presence of a hydrogenation catalyst or with sodium borohydride to afford the corresponding N-protected 3'-deoxy kanamycin A, and
• then removing the residual amino-protecting groups (where present) to give the desired 3'-deoxykanamycin A.