Synthesis of marine natural products that contain a CIS-enamide fragment

Abstract

Indolic enamides are a rare class of marine natural products that have demonstrated a broad range of biological activities, including cytotoxicity and antibacterial activities. Examples of this class of compounds include coscinamides A-C, isolated from the marine sponge Coscinoderma sp., and chondriamides A-C, isolated from the red alga Chondria sp. and Chondria atropurpurea. While a number of synthetic routes targeting the trans-enamide moiety have been reported, little is known regarding the stereoselective synthesis of the indolic cis-enamide fragment. We have made use of a recently reported alkyne hydroamidation methodology to develop a general strategy for the synthesis of cis-enamide containing natural products. This strategy, its strengths and weaknesses, as well as approaches to the synthesis of specific natural products will be presented.