ON THE FATE OF THE TRYPTOPHAN STEREOCENTER DURING THE SYNTHESIS OF HEXACYCLIC ANALOGS OF N-ACETYLARDEEMIN

The reaction between 6-acetyl-3-alkyl-1-ethoxy-3,4,5a,6, 11,11a-hexahy dro-10bH-pyrazino-[2 ',1 '-5,1]pyrrolo[2,3-b]indole-l,4-diones and ant hranilic acid was studied from a stereochemical point of view. Various degrees of epimerization of the tryptophan and alanine stereocenters were observed in compounds with a cis relationship between their H-3 a nd H-11a hydrogen atoms, and stereochemistry was retained in the trans compounds. These observations are explained in terms of steric compre ssion between the C-5=O, C-7-alkyl and C-8=O groups in the hexacyclic reaction products. Acylation at N-2 with o-azidobenzoyl chloride follo wed by an intramolecular aza Wittig reaction afforded the target 10-ac etyl-5,7,8,9a, 10,14b, 15,15a-octahydroindolo[3 '',2 ''-4 ',5 ']pyrrol o[2 ',1 '-3,4]pyrazino[2,1-b]quinazoline-5,8-diones with retention of all stereocenters. (C) 1998 Elsevier Science Ltd. All rights reserved.