Antileukemic Compounds Derived from the Chemical Modification of Macrocyclic Trichothecenes. 1. Derivatives of Verrucarin A

Article abstract of DOI:10.1021/jm00183a018

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