Synthetic approaches to fumitremorgins, tremorgenic micotoxins, from tryptophan in two biomimetic ways are described. I. Oxidative cyclization to β-carboline. Dye-sensitized photo-oxygenation of the 1,2-diisopentyltryptamine (5) gave the 3a-hydroxypyrroloindole (6) which was converted to the β-carboline (8) on warming in trifluoroacetic acid. On the other hand, the 1,2-diprenyltryptamine (3) gave the β-carboline (10) by NBS-CCl_4-AIBN. However, these oxidative cyclizations were not effective to prepare the basic ring system (16) of fumitremorgins from the diketo-piperazines (14,15). II. Preparation of the basic ring system of fumitremorgins. The Pictet-Spengler reaction of the L-tryptophan (18) and isovaler-aldehyde in the presence of trifluoroacetic acid gave the cis β-carboline (19) in 62% and the trans isomer (20) in 33% yields. Condensation of 19 with Z-L-proline chloride followed by the deprotection readily gave the desired cis-cis pentacyclic compound (21). Furthermore, the the 6-methoxy-L-tryptophan (25) has been prepared by the oxidation of the cyclic tautomer (23). The methoxylated pentacyclic compound (29) was prepared from 26 in the similar manner as above. III. Oxidation of the C-ring of the pentacyclic compound (33). The DDQ oxidation of 33 or 35 did not give neither the ketone nor the dehydro derivative of the C-ring. However, the 12-epi compound (39) gave the dehydro derivative (40) on the DDQ oxidation in aqueous acetonitrile. Further investigation to prepare tetrahydro-fumitremorgin B or its epimer from 40 is now in progress.
