On the fate of the tryptophan stereocenter during the synthesis of hexacyclic analogues of N-acetylardeemin

The reaction between 6-acetyl-3-alkyl-1-ethoxy-3,4,5a,6, 11,11a-hexahydro-10bH-pyrazino-[2 ',1 '-5,1]pyrrolo[2,3-b]indole-l,4-diones and anthranilic 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 and H-11a hydrogen atoms, and stereochemistry was retained in the trans compounds. These observations are explained in terms of steric compression 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 followed by an intramolecular aza Wittig reaction afforded the target 10-acetyl-5,7,8,9a, 10,14b, 15,15a-octahydroindolo[3 ",2 "-4 ',5 ']pyrrolo[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.