Synthetic studies toward inducamide C?

Organic & Biomolecular Chemistry Pub Date: 2020-12-08 DOI: 10.1039/D0OB01995J

Abstract

The alkaloid inducamide C is proposed to contain a very rare benzoxazepine ring. Herein, we report that the benzoxazepine ring in inducamide C is unstable and prone to rearrangement, indicating that structural revision of the natural product may be necessary. In a first-generation synthetic approach, attempts to assemble the benzoxazepine by cyclization of 4-hydroxyinducamide A led to the regioisomeric oxepanoindole, a result of the 4-hydroxyindole (C4-OH) undergoing preferential cyclization instead of the desired chlorosalicylic acid C15-OH. A second-generation approach involved dealkylation of O-isopropylinducamide C, but the same oxepanoindole formed via rearrangement of the proposed inducamide C structure. Computational studies validate preferential formation of the oxepanoindole and the lactone in O-isopropylinducamide C is susceptible to nucleophilic attack. Thus, inducamide C is either highly unstable or in need of structural revision.

Graphical abstract: Synthetic studies toward inducamide C
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