PREPARATION OF ALKYL-SUBSTITUTED INDOLES IN THE BENZENE PORTION .13. ENANTIOSPECIFIC SYNTHESIS OF MITOSENE ANALOGS RELATED TO FR-900482 ANDPR-66979

An acid-catalyzed indole formation reaction previously reported by us was successfully applied to the preparation of variously substituted 4 -hydroxy-1H-indoles 11a-g having carbon and/or heteroatom substituents at the benzene portion of the indole ring, using as substrates 3-(4,4 -dialkoxy-1-oxobutyl)-1H-pyrroles 10a-g, which are readily available f rom simple pyrroles in several steps. Employing one of these indoles, 11g, as a starting intermediate, an enantiospecific synthesis of the m itosene analogues 8, 9a and 9b related to antitumor antibiotics FR 900 482 (1) and FR 66979 (2) was achieved by i) condensation of 20 with a chiral aldehyde 21, ii) transformation of 22a and 22b into the tricycl ic compounds 29a and 29b, iii) introduction of the additional one-carb on unit as a formyl group, iv) formation of the aziridine ring, and v) removal of the benzyl protecting group. Elimination of the tert-butyl oxycarbonyl group was also examined to provide the basis for a future project to synthesize 5a, the cross-linkage product of 2 and DNA.