Programmable synthesis of alkaloidal frameworks integrating Michael acceptor generates covalent probes for targeting POLE3 in HBV replication.

ABSTRACT: The growing need for effective HBV treatments and lead compounds with novel mechanisms prompted us to explore synthetic strategies for generating skeletally diverse alkaloidal Michael acceptors. Our approach uniquely embeds Michael acceptors directly within multicyclic alkaloid-inspired frameworks, exploiting the azepinoindole scaffold-a privileged structure in indole alkaloids. A single-step assembly between the versatile intermediate 13 with methyl propiolate 14 or its derivatives enabled the rapid and divergent synthesis of six alkaloidal Michael acceptors (15-20). This strategy facilitated systematic diversification of three-dimensional functional group arrangements and precise tuning of the electronic and steric properties of the embedded α,β-unsaturated carbonyl moieties. The optimal

SUBMITTER: Kaneko N 

PROVIDER: S-EPMC12560046 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature