A method of introducing a 6-position substituent into a 6,9-cyclic acetal of a 5-O-desosaminylerythronolide derivative, characterized by cleaving the cyclic acetal selectively at the 9-position C-O bond; and a process for efficiently synthesizing a 6-O-substituted ketolide derivative which comprises a combination of conversion of each of the 9- and 3-position substituents into a carbonyl group and formation of a 11,12-cyclic carbamate.
