Synthesis of potential antimicrobial oxiranylisobenzofuranones

Five epoxylactones of structural similarity to the antimicrobial sesquiterpene lactone heptelidic acid were synthesized. Starting from perhydroisobenzofuranone, 7a-vinyl- and 7a-allyl-perhydroisobenzofuranone were prepared and oxidized to yield epimeric mixtures of 7a-oxiranyl-and 7a-oxiranylmethylperhydroisobenzofuranones which were separated by chromatography. In a four step synthesis perhydroisobenzofurane-1,7-dione was prepared, transformed to 7-methylene-perhydroisobenzofuranone, and reacted with mCPBA to give the (3a RS, 7 RS, 7a RS)-configurated spirocyclic epoxylactone as a single diastereomer. In a preliminary screening model, epoxylactones proved to be of low toxicity.