Asymmetric Synthesis of Anti-Aldol Segments Via a Non Aldol Route: Synthetic Applications to Statins and (-)-Tetrahydrolipstatin and Enantoselective Total Synthesis of Macrolide (+)-Neopeltolide |
Posted on:2014-02-08 | Degree:Ph.D | Type:Thesis |
University:Purdue University | Candidate:Shurrush, Khriesto A | Full Text:PDF |
GTID:2451390005490334 | Subject:Chemistry |
Abstract/Summary: | |
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. |
Keywords/Search Tags: | Synthesis, Anti-aldol segments, Asymmetric, Via |
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