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

(+/-)-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 C-2-stereochemistry in (+/-)-6. Palladium-catalyzed cyclization of indolyl iodide and the internal C-2 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. (C) 2001 Elsevier Science Ltd. All rights reserved.