CHEMICAL MODIFICATION OF ERYTHROMYCINS .9. SELECTIVE METHYLATION AT THE C-6 HYDROXYL GROUP OF ERYTHROMYCIN-A OXIME DERIVATIVES AND PREPARATION OF CLARITHROMYCIN
Y. Watanabe et al., CHEMICAL MODIFICATION OF ERYTHROMYCINS .9. SELECTIVE METHYLATION AT THE C-6 HYDROXYL GROUP OF ERYTHROMYCIN-A OXIME DERIVATIVES AND PREPARATION OF CLARITHROMYCIN, Journal of antibiotics, 46(4), 1993, pp. 647-660
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).