A diastereoselective synthesis of the polyketide antibiotic citrinin using toluate anion chemistry

Abstract

The diastereoselectivity of various synthetic approaches to (±)-threo-3-(3,5-dihydroxy-2-methyl-phenyl)butan-2-ol (‘Phenol B’)(4), based on reactions of benzyl anions with electrophiles, has been investigated. The anion (9) derived from ethyl 2,4-dimethoxy-6-ethylbenzoate reacted with acetaldehyde to give mainly an erythro-product isolated as the lactone (12); acetylation with acetyl chloride to give a ketone, followed by reduction, gave mainly the required threo-lactone (11). An alternative route was frustrated by decomposition of the benzyl anion derived from 3,4-dihydro-6,8-dimethoxy-3-methyl-1H-2-benzopyran-1-one (17). Reduction of the carbonyl group of the threo-lactone (11) to a methyl gave the dimethyl ether of ‘Phenol B’, which was converted into (±)-citrinin (1).