Development of highly diastereoselective aldol-type synthetic methodologies and the total synthesis of (-)-viridiofungin A
Abstract
Development of two highly diastereoselective synthetic methodologies and the total synthesis of fungal natural product Viridiofungin A have been described. A reductive aldol process that features L-Selectride reduction of chiral or achiral enone followed by reaction of the resulting enolate with optically active alpha-alkoxy aldehydes proceeded with excellent diastereoselectivity has been described. The resulting α,α-dimethyl-β-hydroxy ketones are inherent to a variety of biologically active natural products. The development of a practical synthesis of unique nucleoside derivatives via a TiCl4 promoted multicomponent reaction of optically active dihydrofuran, ethyl pyruvate/glyoxylate, and a TMS protected nucleobase in a single-pot operation has been described as well. A stereoselective synthesis of (-)-viridiofungin A has been accomplished. The convergent synthesis utilized a unique highly diastereoselective multicomponent reaction between optically active phenyldihydrofuran and an α-ketoester to provide two chiral centers including a quaternary carbon center in a single step. Other key steps include an acyloxycarbonium ion mediated tetrahydrofuran ring opening reaction and a Julia-Kocienski olefination.
Degree
Ph.D.
Advisors
Ghosh, Purdue University.
Subject Area
Chemistry|Organic chemistry
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