title: 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, whereas 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.
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D004852:Epoxy Compounds; D006868:Hydrolysis; D006900:Hydroxylation; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004852:Epoxy Compounds