Alkaloids of Vinca rosea L. (Catharanthus roseus G. Don). 38. 4'-Dehydrated derivatives

Abstract

A series of 4'-dehydrated derivatives of various dimeric Vinca alkaloids has been synthesized to further define the structure-activity relationships of Vinca alkaloids with onolytic potency. The concentrated sulfuric acid dehydration in most cases gave mixtures of the 3',4'-and two isomeric 4',20'-alkenes, which were isolated and characterized primarily by proton and 13C NMR. Compound tested for antitumor activity include the three dehydro isomers of 4'-deacetylvinblastine, 4-deacetylvincristine, and 4-deacetylvinblastine-23-amide and some4'-dehydrated derivatives epimeric at C-18'. Generally, the decrease in toxicity imparted by the new double bond was accompained by a decrease in potency. An exception was 3',4'-dehydro-4-deacetylvincristine, which showed a decrease in toxicity and increase in potency against at least one tumor in which vincristine itself has little effect.