Brasilicardin A (Bra A) is a potent immunosuppressive and cytotoxic agent consisting of a disaccharide moiety and an amino acid side chain linked by a terpene core.  The core is comprised of an uncommon anti-syn-anti perhydrophenanthrene structure that places the B ring in a boat-like conformation.  The synthesis of this challenging target is currently unsolved and clinical investigation of Bra A is hindered by a low-yielding fermentation process.  Here, we discuss the convergent synthesis of Bra A analogues that replace the natural core with a tetralin motif.  Modeling this modification relative to the natural product suggests that the sugar and amino acid components are maintained with similar distance and orientation.  Key features of this convergent synthesis include TMS-OTf mediated glycosylation of a chiral tetralol obtained from Noyori asymmetric transfer hydrogenation and Sonogashira coupling of the requisite amino acid precursor which is synthesized in high diastereomeric excess from Garner's aldehyde.

Synthesis of brasilicardin analogs featuring a simplified tetralin core

247th National Meeting (2014)

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