An Approach to the Total Synthesis of Polyether Antibiotics

Author: Wilcox, Craig Stephens

Year: 1979

Degree: Dissertation (Ph.D.)

Advisor: Ireland, Robert E.

Committee Member: Unknown, Unknown

Option: Chemistry

Abstract

Part I. The use of the ester enolate Claisen rearrangement in an approach to polyether antibiotics was investigated. The [3,3] sigmatropic rearrangement of O-silyl ketene acetals derived from the propanoate esters of 1,5- anhydro-hex-1-enitols (pyranoid glycals) provided α-methyl-5, 6-dihydro-2H-pyran-2-acetic acid derivatives. Similarly, 1,4-anhydro-pent-1-enitols provided 2,5-dihydrofuran-2-acetic acid derivatives. The tetrahydro-2-furoate esters of pyranoid glycals provided glycol diethers. The products are models of key structural elements which are present in polyether antibiotics and in other acetogenous natural products of potential medicinal value. The furanoid and pyranoid glycals were conveniently prepared by reductive fragmentation of 2,3-O-(1-methylethylidene)-glycosyl chlorides.

Part II. The preparation of 6-deoxy-k-gulose from D-glucuronic acid is described. Three approaches to the deoxy sugar were explored, and the relative merits of each approach were considered. Several furanoid and pyranoid derivatives of 6-deoxy-L-gulose were described.

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