Synthetic Studies in the Indole Series. Preparation of the Unique Antibiotic Alkaloid Chuangxinmycin by a Nitro Group Displacement Reaction

The total synthesis of the unique sulfur-containing antibiotic indole alkaloid chuangxinmycin is described. This compound, first isolated by Chinese chemists at the Institute of Materia Medica, was assembled from 2,6-dinitrotoluene by a scheme that combines the nitro group displacement reaction with the Leimgruber indole synthesis to produce a 4-sulfur-substituted indole. Further transformations involving acetylation of the indole 3-position, an intramolecular Knoevenagel condensation to dehydrochuangxinmycin methyl ester, and a stereospecific hydrogenation reaction furnish chuangxinmycin methyl ester. The synthesis scheme does establish the cis relationship between the carboxylic acid and methyl group in the natural product.