A simple and efficient pathway for the total synthesis of marine natural products: bengamide E and 5-epi-bengamide E.

Abstract

Total synthesis of the marine natural product bengamide E and 5-epi-bengamide E has been accomplished using two routes: (i) via a polyhydroxy acid precursor involving a total of 16 steps with an overall yield of 17.0% and (ii) via a cyclic lactone precursor with a total of 12 steps and overall 23.0% yield. The key steps involve (1) regioselective p-methoxybenzylidine ring opening, (2) a stereoselective Grignard reaction and (3) olefin cross-metathesis. The total synthesis could provide significant quantities of bengamide E and 5-epi-bengamide E as all the reaction processes were very efficient and the raw materials were inexpensive and highly abundant. The protocol has an advantage over previously reported methods as it provides ready access to the C-5 hydroxy group for further modification and its future structure-activity relationship studies for anti-tumor activity.