Synthetic approaches to fumitremorgins. III: Synthesis of optically active pentacyclic ring systems, and their oxidation at ring C

Pictet-Spengler reaction of L-tryptophan methyl ester (9) and 6-methoxy-L-tryptophan methyl ester (40) with isovaleraldehyde (10) in methylene chloride in the presence of trifluoroacetic acid gave the cis-tetrahydro-β-carboline (11, 41) as the major isomer. The condensation of 11 and 41 with N-benzyloxycarbonyl-L-proline followed by deprotection gave the cis-cis-pentacycles (27, 44) which contain the parent ring system of fumitremorgins. The trans-cis(28), the cis-trans (29, 30) and the trans-trans (31) pentacycles were similarly prepared. Isopentylation of 27 and 44 gave the Na-isopentyl derivatives (52, 53) accompanied with epimerization at the 12-position. Oxidation of 52 and 53 with dichlorodicyano-p-benzoquinone (DDQ) gave the 12, 13-dehydro derivatives (54, 55) which provided demethoxy-13-epi-tetrahydrofumitremorgin B (57) and 17-bromo-13-epi-tetrahydro-fumitremorgin B (58) by N-bromosuccinimide (NBS)-oxidation in aqueous dimethoxyethane. Debromination of 58 gave 13-epi-tetrahydrofumitremorgin B (59).