Synthesis of Phorbol C-ring Analogs: A Biomimetic Model Study on the Phorbol to 12-Hydroxydaphnetoxin Conversion

Abstract

An eight-step synthesis of phorbol C-ring analogs is described. The results of a model study on the phorbol to 12-hydroxy daphnetoxin biomimetic conversion using a C-9 ester-assisted cyclopropyl carbinyl rearrangement are presented. Under the basic conditions used, the dominant reaction pathway is the participation of the C-13 hydroxyl group leading to cleavage of the wrong cyclopropane bond to generate an enone, rather than the desired orthoester. The key step in these synthetic studies is the use of the allyldimethylsilyl functionality as a latent form of hydroxyl group, which facilitates the introduction of the hydroxyl group at cyclic tertiary centers. © 1992, American Chemical Society. All rights reserved.