2 research outputs found
Synthesis of a Potent Vinblastine: Rationally Designed Added Benign Complexity
Many
natural products, including vinblastine, have not been easily subjected
to simplifications in their structures by synthetic means or modifications
by late-stage semisynthetic derivatization in ways that enhance their
biological potency. Herein, we detail a synthetic vinblastine that
incorporates added benign complexity (ABC), which improves activity
10-fold, and is now accessible as a result of advances in the total
synthesis of the natural product. The compound incorporates designed
added molecular complexity but no new functional groups and maintains
all existing structural and conformational features of the natural
product. It constitutes a member of an analogue class presently inaccessible
by semisynthetic derivatization of the natural product, by its late-stage
functionalization, or by biosynthetic means. Rather, it was accessed
by synthetic means, using an appropriately modified powerful penultimate
single-step vindoline–catharanthine coupling strategy that
proceeds with a higher diastereoselectivity than found for the natural
product itself