Towards the synthesis of (-)-callipeltoside A: Stereoselective synthesis of the C1-C14 macrolactone core

摘要

A highly stereoselective synthesis of the C1-C14 macrolactone core of the cytotoxic macrolide (-)-callipeltoside A has been achieved by utilizing an anti-selective aldol reaction and Wittig olefination to introduce an (E)-trisubstituted alkene, chemoselective diisobutylaluminum hydride (DIBAL-H) reduction of the 2,3-epoxy tosylate to install the C13 stereocenter, and intramolecular trapping of the acyl-ketene intermediate by the C13 hydroxy group as key steps. A highly convergent and stereoselective synthesis of the C1-C14 macrolactone core of (-)-callipeltoside A has been achieved by utilizing an anti-selective aldol reaction and Wittig olefination to introduce an (E)-trisubstituted alkene, chemoselective reduction of the 2,3-epoxy tosylate to install the C13 stereocenter, and intramolecular trapping of an acyl-ketene intermediate by the C13 hydroxy group.