Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr‐Catalyzed Dimerization

Longhui Yu; Hiroshige Ogawa; Shangzhao Li; Tsoh Lam Cheung; Wenchao Liu; Dexiu Yan; Yudai Matsuda; Yusuke Kobayashi; Zhihong Guo; Kotaro Ikeda; Trevor A. Hamlin; Ken Yamazaki; Pei-Yuan Qian; Hugh Nakamura

doi:10.1002/anie.202414295

Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr‐Catalyzed Dimerization

Longhui Yu (Co-first Author)
, Hiroshige Ogawa (Co-first Author)
, Shangzhao Li (Co-first Author)
, Tsoh Lam Cheung
, Wenchao Liu
, Dexiu Yan
, Yudai Matsuda
, Yusuke Kobayashi
, Zhihong Guo
, Kotaro Ikeda
, Trevor A. Hamlin
, Ken Yamazaki^*
, Pei-Yuan Qian^*
, Hugh Nakamura^*

^*Corresponding author for this work

Department of Chemistry

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

4 Citations (Scopus)

46 Downloads (CityUHK Scholars)

Abstract

A concise synthetic strategy utilizing a Zr-catalyst for the construction of cyctetryptomycin A and B is herein 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 via 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 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. © 2024 Wiley-VCH GmbH

Original language	English
Article number	e202414295
Number of pages	11
Journal	Angewandte Chemie International Edition
Volume	64
Issue number	2
Online published	31 Aug 2024
DOIs	https://doi.org/10.1002/anie.202414295
Publication status	Published - 10 Jan 2025

Bibliographical note

Full text of this publication does not contain sufficient affiliation information. With consent from the author(s) concerned, the Research Unit(s) information for this record is based on the existing academic department affiliation of the author(s)

Funding

Financial support for this work was provided by a grant from theRGC of the Hong Kong SAR, China (ECS, HKUST 26302024),and start-up funds from HKUST (Project No. R9820) to H.N.; theNational Key Research and Development Program of China(2018YFA0903200), PI Project of Southern Marine Science andEngineering Guangdong Laboratory (Guangzhou) [2021HJ01,SMSEGL20SC01], UGC and RGC of the Hong Kong SARgovernment (16100722, C6026-19G-A, and T11-104/22R) toP.Y.Q.; JSPS KAKENHI (grants numbers JP24K17682) andJP24H01861 (Green Catalysis Science) to K.Y. The computationwas performed using Research Center for Computational Science,Okazaki, Japan (Project: 24-IMS-C118 to K.Y).

Research Keywords

chemoenzymatic
natural product synthesis
Zr-catalyst
dimerization
chemoenzymatic synthesis

Publisher's Copyright Statement

This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

RGC Funding Information

RGC-funded

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10.1002/anie.202414295

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title = "Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr‐Catalyzed Dimerization",

abstract = "A concise synthetic strategy utilizing a Zr-catalyst for the construction of cyctetryptomycin A and B is herein 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 via 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 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. {\textcopyright} 2024 Wiley-VCH GmbH ",

keywords = "chemoenzymatic, natural product synthesis, Zr-catalyst, dimerization, chemoenzymatic synthesis",

author = "Longhui Yu and Hiroshige Ogawa and Shangzhao Li and Cheung, \{Tsoh Lam\} and Wenchao Liu and Dexiu Yan and Yudai Matsuda and Yusuke Kobayashi and Zhihong Guo and Kotaro Ikeda and Hamlin, \{Trevor A.\} and Ken Yamazaki and Pei-Yuan Qian and Hugh Nakamura",

note = "Full text of this publication does not contain sufficient affiliation information. With consent from the author(s) concerned, the Research Unit(s) information for this record is based on the existing academic department affiliation of the author(s)",

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month = jan,

day = "10",

doi = "10.1002/anie.202414295",

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Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr‐Catalyzed Dimerization. / Yu, Longhui (Co-first Author); Ogawa, Hiroshige (Co-first Author); Li, Shangzhao (Co-first Author) et al.
In: Angewandte Chemie International Edition, Vol. 64, No. 2, e202414295, 10.01.2025.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr‐Catalyzed Dimerization

AU - Yu, Longhui

AU - Ogawa, Hiroshige

AU - Li, Shangzhao

AU - Cheung, Tsoh Lam

AU - Liu, Wenchao

AU - Yan, Dexiu

AU - Matsuda, Yudai

AU - Kobayashi, Yusuke

AU - Guo, Zhihong

AU - Ikeda, Kotaro

AU - Hamlin, Trevor A.

AU - Yamazaki, Ken

AU - Qian, Pei-Yuan

AU - Nakamura, Hugh

N1 - Full text of this publication does not contain sufficient affiliation information. With consent from the author(s) concerned, the Research Unit(s) information for this record is based on the existing academic department affiliation of the author(s)

PY - 2025/1/10

Y1 - 2025/1/10

N2 - A concise synthetic strategy utilizing a Zr-catalyst for the construction of cyctetryptomycin A and B is herein 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 via 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 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. © 2024 Wiley-VCH GmbH

AB - A concise synthetic strategy utilizing a Zr-catalyst for the construction of cyctetryptomycin A and B is herein 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 via 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 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. © 2024 Wiley-VCH GmbH

KW - chemoenzymatic

KW - natural product synthesis

KW - Zr-catalyst

KW - dimerization

KW - chemoenzymatic synthesis

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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85208203238&origin=recordpage

U2 - 10.1002/anie.202414295

DO - 10.1002/anie.202414295

M3 - RGC 21 - Publication in refereed journal

C2 - 39216012

SN - 1433-7851

VL - 64

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 2

M1 - e202414295

ER -

Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr‐Catalyzed Dimerization

Abstract

Bibliographical note

Funding

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

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