Total Synthesis of the Indole Alkaloid (±)- and (+)-Methyl N-Decarbomethoxychanofruticosinate

摘要

Methyl N-decarbomethoxychanofruticosinate (1; Figure 1) belongs to a growing family of indole alkaloids with more than twenty members, namely methyl chanofruticosinates (some of these members were also called kopreasins, prunifolines,and flavisiamines by different isolation groups). These alkaloids have been isolated from a variety of Kopsia (Apocynaceae) species, which are widely distributed in tropical Asia and have been historically used for the treatment of diseases and symptoms like pharyngitis, tonsillitis, rheumatoid arthritis, and ulcerated noses in tertiary syphilis. Preliminary biological studies of these natural products indicated that their existence is partially responsible for the medicinal properties of the Kopsia (Apocynaceae) species. For example, 1 has showed significant antitussive activity in a citric acid induced guinea pig cough model, which might be associated with the activation of δ-opioid receptors. The same alkaloid also displayed relaxation activity against phenylephrine-induced contractions of rat aortas, and is the most potent agent among eleven methyl chanofrutico- sinate alkaloids tested.