On the Chemistry of Resiniferonol I. Preparation of Resiniferonol, Synthesis of Homologous Aliphatic Resiniferonol-9,13,14-orthoesters and Some of their Bioactivities

Abstract

The preparation of the daphnane prototype polyfunctional diterpene resiniferonol from resiniferatoxin (1) contained in latex from Euphorbia unispina or E. poisonii was modified to convert in an ‘early’ fraction of the acetone extract the extremely irritant 1 to the much less irritant 9,13.14-ortho(phenylacetate) 2 by transesterification. 2 was obtained in good yields and can be handled conveniently to prepare resiniferonol as reported previously. By esterification of resiniferonol with homologous straight chain aliphatic acids from C2, to Cl8 resiniferonol-14,20-diacylates were prepared. Treatment of the diacylates with perchloric acid/methanol yielded by intramolecular formation of the orthoester function the corresponding 9,13,14-orthoester-20-acylates. They were cleaved selectively by base catalysed transesterification to obtain the resiniferonol-9,13,14-orthoacetate (3), -hexanoate (4), -decanoate (5), -tetradecanoate (6) and -octadecanoate (7). On the mouse ear, unexpectedlythey exhibit only weak irritant activity and on the mouse back skin practically no tumor promoting activity. © 1993, Walter de Gruyter. All rights reserved.