Mycalolide A, a marine macrolides constructed around a 25-membered lactone and a polypropionate structure, has shown a diversity of biological activities, such as antifungal and antileukemic properties. These structural features and bioactivity have prompted a number of research groups to propose strategies towards its synthesis. We have also been working towards the synthesis of mycalolide A using an epoxide-based approach for the stereoselective preparation and subsequent coupling of the C21-C29 and C30-C34 polypropionate fragments. The required precursors were prepared employing our regioselective preparation and cleavage of enantiomeric 3,4-epoxy alcohols as the key steps for their elaboration. This was done controlling the absolute configuration of the epoxide precursors and the regioselectivity of the ring opening reaction with alkynyl alanes or alkenyl Grignard reagents in a reiterative fashion. This strategy provided an aldehyde containing the C30�C34 carbons that was synthesized in 5 steps, while a syn,anti,cisepoxysilane stereotriad containing the C21�C25 unit was prepared the 4 steps. The aldehyde fragment has also been used in the elaboration of the unrelated and structurally simpler Crocacin C polypropionate target. The details and recent advances towards these targets will be presented. Work supported by the NIH SCORE (2S06GM-08102-29) and NIH RISE (1R25-GM-61151-01A1) Programs.

Studies toward the synthesis of mycalolide A and Crocacin C polypropionate fragments employing an epoxide-based approach

248th National Meeting (2014)

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