Antileukemic compounds derived from the chemical modification of macrocyclic trichothecenes. 1. Derivatives of verrucarin A

Abstract

Verrucarin A (2) was epoxidized to give the .beta.-9,10-epoxide 7 (major product) and .alpha.-9,10-epoxide 9 (minor product). The .beta.-epoxide 7 and its acetate 8 exhibit high in vivo antileukemic activity against P-388 mouse leukemia, while 2 and 9 are inactive. Epoxidation of verrucarin B (3) and roridin A (1) to their respective .beta.-9,10-epoxides (11 and 12, respectively), also yields compounds with substantially increased activity. Allylic alcohols derived from 2, .alpha.-C8 (20), .beta.-C8 (14) and C16 (15), were synthesized and tested; only 15 exhibited substantial in vivo activity.