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Updated: May 18, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis and structure-activity relationship of vicenistatin, a cytotoxic 20-membered macrolactam glycoside
Hayato Fukuda1, Yuko Nishiyama, Shiina Nakamura
1Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-9578, Japan.
Abstract:
We have developed two syntheses of vicenistatin and its analogues. Our first-generation strategy included the rapid and sequential assembly of the macrocyclic lactam by using an intermolecular Horner-Wadsworth-Emmons reaction between the C3-C13 fragment and the C1-C2, C14-C19 fragment, followed by an intramolecular Stille coupling reaction. The second-generation strategy utilized a ring-closing metathesis of a hexaene intermediate to generate the desired 20-membered macrolactam. This second-generation strategy made it possible to prepare synthetic analogues of vicenistatin, including the C20- and/or C23-demethyl analogues. Evaluation of the cytotoxic effect of these analogues indicated the importance of the fixed conformation of aglycon for determining the biological activity of the vicenistatins.
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