Efficient synthesis of dl-malyngolide

Abstract

PART I. Malyngolide, an antibiotic from the marine blue-green alga Lyngbya majuscular Gomont, has been synthesized from 2-carbomethoxycyclopentanone in a 60% overall yield in five steps. 2-Carbomethoxycyclopentanone was converted to δ-lactone via alkylation and Baeyer-Villiger oxidation. The lactone could be converted to malyngolide by a sequence of methylation,hydrolysis of methyl ester, and reduction. PART II. The use of tri-n-butylphosphine in place of triphenylphosphine for conversion of carboxylic acid into S-alkyl thiol esters and the scope and the limitation of the reaction have been studied. Reaction of carboxylic acid with tri-n-butylphosphine and primary dialkyl disulfide in methylene chloride at room temperature affords corresponding thiol esters in high yields. The reaction is very sluggish with secondary disulfide and does occur with tertiary disulfide. However, reaction of carboxylic acid with tri-n-butylphosphine and secondary disulfide under the influence of ultrasonic irradiation affords the secondary alkyl thiol esters in high yields. The formation of tertiary alkyl thiol esters under the influence of ultrasound is ineffective.