Synthesis of (14R)- and (14S)-14-De(hydroxymethyl)-14-hydroxymycaminosyl Tylonolides

Abstract

Abstract The title compounds 29 and 19 have been prepared from mycaminosyl tylonolide 9,20-bis(ethylene acetal) via 9 (for 19) and 13 steps (for 29). The key step in the synthesis of 19 is Baeyer-Villiger reaction applied to 2′,4′-di-O-acetyl-3-O-t-butyldimethylsilyl-23-deoxy-23-oxomycaminosyl tylonolide 9,20-bis(ethylene acetal), and the desired 14-O-formyl derivative is obtained with other products including 12,13-epoxy and 14-C-carboxylic acid. The key step in the synthesis of 29 is Mitsunobu reaction applied to (14S)-2′,4′-di-O-acetyl-3-O-t-butyldimethylsilyl-14-de(hydroxymethyl)-14-hydroxymycaminosyl tylonolide 9,20-bis(ethylene acetal), and the desired (14R)-acyloxy product is obtained by inversion at C-14, with other compounds including 10(11), 12(22), 13(14)-triene and 12-acyloxy-10(11),13(14)-diene.