Affiliation:
1. Drug Discovery & Development Platform, Science for Life Laboratory, Department of Organic Chemistry, Stockholm University, Tomtebodavägen 23a, 17165 Solna, Sweden
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.
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science