In our environment there exist a wide variety of natural products, many of them from oceanic origin. Among these, the macrolides represent a large family of compounds that have shown a wide range of biological activity. Because of this, and their relatively complex chemical structures, the synthetic organic community has devoted enormous efforts towards their elaboration and modification. Fusetani and co-workers reported the isolation of mycalolide A from a sponge of the genus <i>Mycale sp</i>. Mycalolide A, a 25-membered macrolide containing a polypropionate subunit that exhibits potent antifungal activity against a wide array of pathogenic fungi and cytotoxicity toward B-16 melanoma cells and inhibits the actimyosin Mg<sup>2+</sup>-ATPase. Different approaches for the synthesis of mycalolide A and its polypropionate chain have been reported, although aldol-related approaches have been the most used. In this regard, our laboratory has developed a reiterative epoxide-based methodology for the stereoselective elaboration of polypropionate modules. This method encompasses a stereoselective epoxidation followed by a regioselective epoxide opening. This substrate controlled method allows the elaboration of the required stereogenic centers from the first epoxidation to the subsequent steps. Using this strategy, we prepared a terminal epoxide containing the C21-C25 polypropionate fragment of mycalolide A, synthesized in 8 steps in a 24% overall yield. This approach represents a suitable method to synthesize the first mycalolide A stereotriad with high stereoselectivity. This precursor is being used on the elaboration of the C21-C29 polypropionate fragment employing our epoxied-based methodology. The results and details of this study will be presented. Supported by NIH SCORE (2S06GM-08102-29) and NIH MARC (5T34GM007821) Programs.

Synthesis of the mycalolide A polypropionate chain using an epoxide-based approach

251st National Meeting (2016)

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