I. Cycloaddition reactions of N-sulfonyl-4-(ethoxycarbonyl)-1-aza-1,3-butadienes. II. Studies on the total synthesis of rhizoxin and related agents: C13-C26 fragment
Abstract
The cycloaddition reactions of N-sulfonyl-4-ethoxycarbonyl-1-aza-1,3-butadienes with olefins are regio- and diastereoselective. The addition of an electron withdrawing substituent (C4-CO$\sb2$Et) accelerated the rate of reaction. The scope of participation of N-sulfonyl-4-ethoxycarbonyl-1-aza-1,3-butadienes in (4+2) cycloaddition reactions with dienophiles is detailed and allows the stereocontrolled synthesis of highly substituted 1,2,3,4-tetrahydropyridines. Rhizoxin (NSC-33298) is an antifungal, antitumor agent isolated from Rhizopus chinensis and is the most extensively examined member of a new class of agents. Unique structural features of rhizoxin include a triene oxazole side chain, eleven stereocenters and a sixteen-membered macrocyclic lactone. Studies on the preparation of the lower subunit of rhizoxin (C13-C26) in homochiral form is described. The approach is based on model studies, which are also described, and key elements of the synthesis of the C13-C26 fragment include the stereoselective introduction of the C18-C19 trisubstituted olefin through the use of a Wadsworth-Homer-Emmons condensation and the diastereoselective introduction of the C17 stereocenter by a hydroxyl-directed reduction of a $\beta$-hydroxy ketone.
Degree
Ph.D.
Advisors
Boger, Purdue University.
Subject Area
Organic chemistry
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