Synthesis and Antiproliferative Activity of 9‐Formyl and 9‐Ethynyl Noscapines

Abstract Appending functional groups to the core skeleton of natural α‐noscapine, an FDA approved cough medicine, resulted in analogues with anticancer activity. In this study, we report the synthesis and antiproliferative activity of 9‐formyl and 9‐ethynylnoscapines. 9‐Formylnoscapine 5 was synthesized from 9‐bromonoscapine 2c via a three‐step reaction sequence involving palladium catalysed Heck reaction with ethyl acrylate leading to noscapinoid 7 , dihydroxylation of 7 with OsO 4 and oxidative cleavage of diol 8 . Further, Seyferth‐Gilbert homologation of 9‐formylnoscapine using Bestmann ‐ Ohira reagent resulted in 9‐ethynylnoscapine 6 in excellent yield. Antiproliferative activity screening of new noscapinoids 5‐7 against NCI60 human tumor cell lines resulted in 9‐ethynylnoscapine 6 as a potent anticancer agent with the lowest mean percentage growth against the full 60‐cell line panel.