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

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.

SUBMITTER: Bengtsson C

PROVIDER: S-EPMC10304315 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

Bengtsson Christoffer C Gravenfors Ylva Y

Molecules (Basel, Switzerland) 20230616 12

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-<i>e</i>]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 ...[more]

PMID: 37375372

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