Semisynthetic macrolide antibacterials derived from tylosin. Synthesis of 3-O-acetyl-23-O-demycinosyl-4″-O-isovaleryltylosin and related compounds, as well as the 12,13-epoxy derivatives

Abstract

Selective acylation techniques have been developed that enable the synthesis of 3-O-acetyl-4″-O-isovaleryltylosin and 3-O-acetyl-23-O-demycinosyl-4″-O-isovaleryltylosin to be carried out in an efficient manner starting from tylosin. The syntheses of the 2′-O-acetyl, 23-O-acetyl, and 2′,23-di-O-acetyl derivatives of the latter are also described. The synthesis of key hydrazones is also described. The regio- and stereo-selective epoxidation of tylosin and its acyl derivatives afforded the 12,13-epoxy analogues, which were used to synthesize novel acylated 12,13-epoxy derivatives of 23-O-demycinosyltylosin.