Bidirectional synthesis of montamine analogs

Reported herein is a bidirectional synthesis of symmetric N,N′-diacyl hydrazide compounds closely resembling the alkaloid natural product montamine. In the process, di-tert-butyl hydrazine-1,2-dicarboxylate was smoothly dialkylated with alkyl halides, then Boc deprotected and acylated with an acetate-protected acid chloride derived from ferulic acid. After acetate removal, simple montamine analogs were obtained in excellent overall yields. Fischer indole synthesis with 4-methoxyphenylhydrazine hydrochloride and dihydrofuran provided 5-methoxytryptophol, which was then elaborated to the 1,2-bis(5-methoxyindol-3-yl)hydrazide structure bearing the substitution pattern found in montamine.