Highly selective auxiliary-mediated acetate aldol additions and progress towards the total synthesis of (-)-brevenal

Highly selective auxiliary-mediated acetate aldol additions and progress towards the total synthesis of (-)-brevenal Public Deposited

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Creator

Shamszad, Mariam
- Affiliation: College of Arts and Sciences, Department of Chemistry

Abstract

The development of a highly selective acetate aldol addition using chlorotitanium enolates of novel mesityl-substituted N-acetyloxazolidinethione and N-acetylthiazolidinethione auxiliaries is herein described. This method proceeds in high yields and diastereoselectivity for aliphatic, aromatic,beta-unsaturated, and non-racemic aldehydes, efficiently generating the beta-hydroxycarbonyl subunit, prevalent in polyketide-derived natural products. Efforts towards the total synthesis of the marine pentacyclic polyether, brevenal, are also described. Brevenal has been found to counteract the toxic effects of the brevetoxins, a family of molecules also produced by Karenia brevis, alleviating respiratory distress. A highly convergent route to brevenal is herein illustrated in which a Horner-Wadsworth-Emmons reaction is used to couple two key complex cyclic ether fragments. In addition, an asymmetric glycolate alkylation/ring-closing metathesis strategy has been employed to synthesize two of the five rings.

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