New total synthesis of (±)-, (-)- and (+)-chuangxinmycins

Article abstract of DOI:10.1016/S0040-4020(01)01068-7

(±)-2-Hydroxy-3-(1H-4′-iodoindol-3′-yl)butanoate 6 was stereoselectively converted into the (±)-(2,3)-syn-2-thioacetoxy ester 13 with retention of C₂-stereochemistry in (±)-6. Palladium-catalyzed cyclization of indolyl iodide and the internal C₂ thiol group of the substrate (±)-14 gave the (±)-cis methyl ester 2 of natural chuangxinmycin (1). Stereoselective total syntheses of (-)-(4S,5R)- and (+)-(4R,5S)-chuangxinmycins 1 were achieved based on the enzymatic syntheses of (2R,3S)- and (2S,3R)-epoxy butanoates 9, respectively. Chiral intermediates such as (2R,3S)- and (2S,3R)-2-hydroxy-3-(1H-4′-iodoindol-3′-yl)butanoate 6 for the chiral synthesis of (-)- and (+)-1 were also obtained by the enantioselective hydrolysis of the corresponding acetate (±)-16 by lipase.