The synthesis of some cyclopentanoid natural products

• Main Author: MacPherson, David Timothy
• Published: Sheffield Hallam University 1984
• Subjects: 547; Organic chemistry
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.349599

The rapidly expanding area of research into cyclopentanoid natural products is briefly reviewed by reference to some of the more important classes of such natural products. Some of the more general procedures that have been developed for the construction of cyclopentane rings are discussed. The eight step synthesis of a highly functionalised bicyclo[3.3.0]octane derivative from readily available methyl 2-oxocyclopentanecarboxylate is described. The key feature of this synthesis involves the construction of a cyclopentane ring through intramolecular Wittig reaction using (methylthio) or (phenylthio) substituted vinyl phosphonium salts, (developed earlier in our laboratories).This bicyclo [3.3.0] octane derivative contains useful functionality in both rings and has been used in syntheses of several natural products. A simple three step procedure which uses the structural features of the bicyclo[3.3.0] octane unit to achieve stereocontrol led to a precursor of the beetle defensive secretion chrysomelidial. A nine step procedure involving the conversion of a ketone to an alpha,beta unsaturated ester and deconjugation of this ester to the beta,alpha-unsaturated isomer as key features led to a bicyclo [3.0.0] octane precursor to the iridoid glucoside loganin. Two formal syntheses of hirsutene the parent hydrocarbon of the hirsutane family of natural products were developed. Both syntheses involved regiospecific alpha-alkylation of the anion derived from a vinyl sulphone to introduce the third ring necessary for hirsutene. Such an alkylation with 2-(2-iodoethyl)-1,3-dioxalane led to a known bicyclo [3.3.0]octane precursor to hirsutene. A similar alkylation with 5-iodo-2-pentyne led to an enyne which underwent cationic cyclization in formic acid to give a linearly fused tricyclopentanoid system. This product was converted in one step to an immediate precursor to hirsutene. Possible further uses of this highly functionalised bicyclo [3.3.0] octane derivative are discussed. An intermediate involved in the preparation of the key bicyclo [3.3.0] octane derivative was converted to an immediate precursor to the antitumour agent sarkomycin.