Concise synthesis and antitumor activity of Bengamide e and its analogs

Article abstract of DOI:10.1016/j.tet.2012.11.004

Bengamide E (1a) and C-2 epimer (1b), free hydroxyl analogs (1c) and (1d), and shorter chain analog (1e) were synthesized by utilizing (2R,3S,4R)-2,3,4- tris(benzyloxy)hex-5-enal (2a) as the chiral building block. Preliminary biological studies revealed that only compound 1c showed slightly weaker activity than Bengamide E (1a) against MDA-MB-453 human breast carcinoma cells, MCF-7 human breast cancer cells and HCT-116 colon cancer cells, with the others being inactive. These results suggest that the correct stereochemistry at C-2, the alkylation on C-2 hydroxyl group, as well as the length of the carbon chain of Bengamide E are critical for structural recognition and binding to the target(s).