Synthesis 2019; 51(11): 2237-2251
DOI: 10.1055/s-0037-1611779
review
© Georg Thieme Verlag Stuttgart · New York

FR901483: Synthetic Efficiency Remains a Challenge

Zhuwei Ruan
a  Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry (CAS), 345 Lingling Road, Shanghai 200032, P. R of China   Email: rhong@sioc.ac.cn
b  University of Chinese Academy of Sciences, 19A Yuqiang Road, Beijing 100049, P. R. of China
,
Cheng Li
c  WuXi AppTec, 666 Gaoxin Avenue, Wuhan 430075, P. R. of China
,
Defeng Shen
a  Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry (CAS), 345 Lingling Road, Shanghai 200032, P. R of China   Email: rhong@sioc.ac.cn
b  University of Chinese Academy of Sciences, 19A Yuqiang Road, Beijing 100049, P. R. of China
,
Sha-Hua Huang*
a  Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry (CAS), 345 Lingling Road, Shanghai 200032, P. R of China   Email: rhong@sioc.ac.cn
d  School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai 201418, P. R. of China   Email: shahua@sit.edu.cn
,
Ran Hong*
a  Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry (CAS), 345 Lingling Road, Shanghai 200032, P. R of China   Email: rhong@sioc.ac.cn
› Author Affiliations
Financial support from the National Natural Science Foundation of China (21672246 to R.H.), the Collaborative Innovation Program of Shanghai Institute of Technology (XTCX2015-16 to S.S.H.), and the Key Research Program of Frontier Sciences (QYZDY-SSWSLH026) and the Strategic Priority Research Program (XDB20020000 to R.H.) of the Chinese Academy of Sciences is greatly appreciated.
Further Information

Publication History

Received: 08 February 2019

Accepted after revision: 05 March 2019

Publication Date:
24 April 2019 (eFirst)

Abstract

FR901483 is a unique alkaloid bearing an aza-tricyclic structure, a phosphate group, and a congested tertiary nitrogen center. This alkaloid was reported to be a potent immunosuppressant with antimetabolite ability. The unprecedented architecture has captured imagination of synthetic chemists since its isolation in 1996. To date, ten total or formal syntheses and several synthetic approaches to access the tricyclic core skeleton have been reported. In this review, we highlight the novel synthetic methods and strategies and discuss the synthetic challenge for meeting the criteria of drug development.

1 Introduction

2 Bioinspired Total Synthesis of FR901483

3 Non-bioinspired Approaches toward FR901483

4 Various Tactics for Accessing the Core Skeleton

5 Challenges for Efficiency

 
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