2. Academic Validation
  3. Asymmetric Total Synthesis of Cytotrienin A: Late-Stage Installation of C11 Side Chain onto the Macrolactam Scaffold

Asymmetric Total Synthesis of Cytotrienin A: Late-Stage Installation of C11 Side Chain onto the Macrolactam Scaffold

  • Angew Chem Int Ed Engl. 2023 Jul 17;62(29):e202303140. doi: 10.1002/anie.202303140.
Yuki Tateishi 1,  Ryo Sato 1,  Shingo Komatsu 1,  Masatsugu Noguchi 1,  Shota Nagasawa 1,  Yusuke Sasano 1,  Naoki Kanoh 1 2,  Yoshiharu Iwabuchi 1
Affiliations

Affiliations

  • 1 Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
  • 2 Current address: School of Pharmacy and Pharmaceutical Sciences, and Institute of Medicinal Chemistry, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
PMID: 37212460 DOI: 10.1002/anie.202303140
Abstract

Cytotrienin A, an ansamycin-class Antibiotic, exhibits potent apoptosis-inducing activity and has attracted much attention as a lead compound for Anticancer drugs. Herein, we report a new asymmetric synthetic route to cytotrienin A, employing an unexplored approach involving the late-stage installation of a C11 side chain onto the macrolactam core. In this strategy, we utilized the redox properties of hydroquinone and installed a side chain on the sterically hindered C11 hydroxy group by the traceless Staudinger reaction. This study also demonstrated that the boron-Wittig/iterative Suzuki-Miyaura cross-coupling sequence was effective for the concise and selective construction of the (E,E,E)-conjugated triene moiety. The developed route opens new opportunities for the structure-activity relationship studies of the side chains of these ansamycin Antibiotics and the preparation of Other synthetic analogs and chemical probes for further biological studies.

Keywords

Acylation; Cross-Coupling; Macrocycles; Redox Chemistry; Total Synthesis.

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