ArticleJACS Au2025
Multicomponent Reaction-Enabled Semisynthesis of Taxanes Yields an Analogue with Reduced Chemotherapy-Induced Neuropathy.
Article in JACS Au, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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Corrections and comments
- Erratum issued
Authors and funding
14 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy-induced peripheral neuropathy (TIPN) affects up to 97% of patients receiving taxane regimens, yet no single-agent solution exists. Current practice relies on coadministration of pain-modulating agents with taxanes, which adds complexity, potential drug-drug interactions, and patient-compliance hurdles. To address TIPN at its source, we set out to create a taxane analogue that intrinsically prevents neuropathy while retaining anticancer potency. Because building even small libraries of taxane derivatives via traditional semisynthetic or total-synthesis routes is laborious and step-intensive, we developed a late-stage, multicomponent reaction (MCR)-based platform on baccatin III for rapid, modular side-chain assembly. Using this approach, we synthesized over 30 C13-diversified taxanes in two steps with excellent stereocontrol and overall yields (35-68%). Lead compound
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