CHEMICAL MODIFICATION OF ERYTHROMYCINS .9. SELECTIVE METHYLATION AT THE C-6 HYDROXYL GROUP OF ERYTHROMYCIN-A OXIME DERIVATIVES AND PREPARATION OF CLARITHROMYCIN

Although erythromycin A contains five hydroxyl groups, regioselective methylation at the C-6 hydroxyl group was achieved to the extent of 90 % when a 9-O-substituted erythromycin A 9-oxime was employed as substr ate. The methylation and its selectivity are dependent on an O-protect ing group at the 9-oxime, solvent, base, and methylating reagent. In p articular, the use of a polar aprotic solvent is indispensable for the methylation. Among the 9-oxime derivatives, 3'-N-bis(benzyloxycarbony l)-N-demethylerythromycin A 9-[O-(2-chlorobenzyl)oxime] was the most i mportant intermediate for the synthesis of clarithromycin (6-O-methyle rythromycin A).