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Updated: Jun 14, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr-Catalyzed Dimerization
Longhui Yu1, Hiroshige Ogawa1, Shangzhao Li1
1The Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon, Hong Kong SAR, China.
Abstract:
A concise synthetic strategy utilizing a Zr catalyst for the construction of cyctetryptomycin A and B is reported. Cyctetryptomycin A and B are recently isolated, complex tetrameric natural products for which total synthesis has not been previously reported. This study presents a practical approach for the construction of two consecutive quaternary carbon centers with a Zr catalyst. Furthermore, the first total synthesis of cyctetryptomycin A and B was achieved by this Zr-catalyzed radical coupling. The radical dimerization reaction mediated by the Zr catalyst required 1,2-bis(diphenylphosphino)ethane (dppe) as an indispensable additive. Through both experimental and theoretical investigations into the mechanism of this Zr-catalyzed reaction, the specific role of dppe was elucidated. In addition, the synthetic approach was extended to enable the practical synthesis of other dimeric natural products, including tetratryptomycin A, dibrevianamide F, and ditryptophenaline. Finally, the synthetic mechanism of cyctetryptomycin A and B, through the oxidative macrocyclization of tetratryptomycin A by CttpC, was newly elucidated by both experimental and docking simulations.
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