Total Synthesis of (-)-Thiangazole and Structurally Related Polyazoles

Article abstract of DOI:10.1021/jo00127a030

Thiangazole was reported to be an extremely potent, nontoxic inhibitor of HIV-1 in MT4 cell assays.By employing a strategy of selective oxazoline-thiazoline interconversions, we have accomplished a total synthesis of the natural product in 16 steps and 1.1percent overall yield from (S)-α-methylserine.This new methodology is especially useful for the preparation of analogs of thiangazole and structure-activity studies.Our preliminary biological testing of (-)-thiangazole revealed a high level of cytotoxicity that was considerably reduced in the oxazoline-containing analogs.