The synthesis of macrolides continues as an attractive area of organic synthesis. Their biological activity and therapeutic potential makes them atracctive targets. The polypropionate unit, which consists of an array of alternating methyl and hydroxy groups on a chain with a distinct configuration, is common in many of these targets. Although a number of synthetic approaches to polypropionates have been implemented, aldol related strategies still predominate. In this regard we have developed a reiterative epoxide-based methodology for polypropionate construction. This non-aldol approach combines a sequence of a stereoselective epoxidation of 3,4-alkenols followed by an epoxide ring opening with an alkynyl alane or alkenyl Grignard reagent. This has been applied for the construction of several termini differentiated polypropionate fragments. Here we extend this methodology for the elaboration of two new targets, the mycalolide A and the related crocacin C polypropionate fragments. For this we worked in the construction of the C21-C29 and C30-C34 fragments employing our epoxide based strategy. This approach provided an aldehyde containing the C30–C34 carbons synthesized and the <i>syn,anti,cis</i> epoxysilane stereotriad containing the C21–C25 unit for their further coupling. This aldehyde fragment was also used as a common precursor for the elaboration of the crocacin C polypropionate target. The details and latest advances towards these targets will be presented.<br/>Supported by NIH SCORE (2S06GM-08102-29) and NIH RISE (2R25GM061151-13) programs.

Epoxide-based methodology for the non-aldol construction of the mycalolide A and crocacin C polypropionate fragments

251st National Meeting (2016)

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