Asymmetric Synthesis of Anti-Aldol Segments Via a Non Aldol Route: Synthetic Applications to Statins and (-)-Tetrahydrolipstatin and Enantoselective Total Synthesis of Macrolide (+)-Neopeltolide

Khriesto A Shurrush, Purdue University

Abstract

The asymmetric synthesis of anti-aldol segments via a non-aldol route is described. The strategy involves a highly diastereoselective synthesis of functionalized tetrahydrofuran derivatives from optically active 4-phenylbutyrolactone. Treatment of the tetrahydrofuran derivatives with a Lewis acid and acetic anhydride provided the corresponding ring opened styrene derivatives. Oxidative cleavage of the styrene derivatives provides access to the anti-aldol segments. The utility of this methodology was demonstrated by the synthesis of statine derivatives and pancreatic lipase inhibitor, (-)-tetrahydrolipstatin. The asymmetric total synthesis of antiproliferative macrolide (+)-neopeltolide has been completed. The stereochemically defined trisubstituted tetrahydropyran ring was constructed via a catalytic hetero Diels-Alder reaction creating two new chiral centers in a highly diastereoselective manner. The other key features of this synthesis involve Brown's asymmetric allylation to install the requisite C11 and C13 stereocenters. The synthesis of the oxazole side chain featured a hydrozirconation of an alkynyl stannane to establish the Z stereochemistry, followed by a palladium catalyzed cross coupling to introduce the desired Z olefin in the oxazole side chain.

Degree

Ph.D.

Advisors

Ghosh, Purdue University.

Subject Area

Organic chemistry

COinS