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

The preparation o f the daphnane proto type polyfunctional diterpene resiniferonol from resiniferatoxin (1) contained in latex from Euphorbia unispina or E. poisonii was modified to con­ vert in an 'early ' fraction o f 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 o f resi­ niferonol with hom ologous straight chain aliphatic acids from C2 to C 18 resiniferonol-14,20diacylates were prepared. T reatm ent o f the diacylates with perchloric acid/m ethanol yielded by intram olecular form ation o f the o rthoester function the corresponding 9,13,14-orthoester20-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, unexpectedly they exhibit only weak irritan t activity and on the m ouse back skin practically no tum or prom oting activity.