SYNTHETIC STUDIES OF TRICHOTHECENES
Abstract
The trichothecenes are a group of sesquiterpene alcohols and esters which exhibit a broad range of biological activity. Many studies of the biology and chemistry of this class have appeared. Chapter 1 presents a comprehensive review of this literature. The ultimate goal of this research is to develop an efficient enantiospecific synthesis of anguidine. A flexible synthesis of this important trichothecene could provide access to a host of natural and synthetic trichothecenes for medicinal evaluation. Our approach to anguidine involves four stages: (1) the synthesis of an optically active C ring precursor; (2) stereospecific annelation of the A ring to this precursor; (3) biomimetic cyclization of the B ring; (4) final decoration of the skeleton. Microbial reductions of 2,2-disubstituted-cyclopentanediones were explored as a method of generating the required chiral starting material. The ketol derived from 2-allyl-2-methylcyclopentanedione was elaborated to a bicyclic lactone which possessed the correct stereochemistry for the trichothecene C ring. Spiroannelation of the hydroxymethylene derivative of this lactone proceeded in excellent yield to furnish the A-C ring unit for biomimetic closure. An alternative cyclization mode was found to predominate over the desired closure. After some difficulty this was overcome and the trichothecene skeleton was produced in optically pure form.
Degree
Ph.D.
Subject Area
Organic chemistry
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