Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug

Molecules. 2023 Jun 16;28(12):4818. doi: 10.3390/molecules28124818.

Abstract

The construction of duocarmycin-like compounds is often associated with lengthy synthetic routes. Presented herein is the development of a short and convenient synthesis of a type of duocarmycin prodrug. The 1,2,3,6-tetrahydropyrrolo[3,2-e]indole-containing core is here constructed from commercially available Boc-5-bromoindole in four steps and 23% overall yield, utilizing a Buchwald-Hartwig amination followed by a sodium hydride-induced regioselective bromination. In addition, protocols for selective mono- and di-halogenations of positions 3 and 4 were also developed, which could be useful for further exploration of this scaffold.

Keywords: 1,2,3,6-tetrahydropyrrolo[3,2-e]indole; duocarmycin; prodrug; selective halogenation.

MeSH terms

  • Amination
  • Duocarmycins
  • Prodrugs*

Substances

  • Duocarmycins
  • Prodrugs

Grants and funding

This research received no external funding.