Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug.

Bengtsson C, Gravenfors Y

Molecules 28 (12) - [2023-06-16; online 2023-06-16]

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.

Drug Discovery and Development (DDD) [Collaborative]

PubMed 37375372

DOI 10.3390/molecules28124818

Crossref 10.3390/molecules28124818

pmc: PMC10304315
pii: molecules28124818

Publications 9.5.0