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Updated: Dec 6, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Pharmacophore-Directed Retrosynthesis Applied to Ophiobolin A: Simplified Bicyclic Derivatives Displaying Anticancer
Yongfeng Tao, Keighley N Reisenauer, Marco Masi1
1Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant' Angelo, Naples, Italy.
Abstract:
Pharmacophore-directed retrosynthesis applied to ophiobolin A led to bicyclic derivatives that were synthesized and display anticancer activity. Key features of the ultimate defensive synthetic strategy include a Michael addition/facially selective protonation sequence to set the critical C6 stereocenter and a ring-closing metathesis to form the cyclooctene. Cytotoxicity assays toward a breast cancer cell line (MDA-MB-231) confirm the anticipated importance of structural complexity for selectivity (vs MCF10A cells) while C3 variations modulate stability.
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