Semisynthesis of CRV431

被引：5

作者：

Li, Feng-Xia ^{[1
,2
]}

Zhang, Qing-Zhou ^{[1
,2
]}

Li, Shi-Jun ^{[3
,4
]}

Lin, Guang ^{[1
,2
]}

Huo, Xiang-Yu ^{[1
,2
]}

Lan, Yu ^{[3
,4
,5
,6
]}

Yang, Zhen ^{[1
,2
,7
,8
,9
]}

机构：

[1] Peking Univ, Sch Chem Biol & Biotechnol, State Key Lab Chem Oncogen, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China

[2] Peking Univ, Sch Chem Biol & Biotechnol, Lab Chem Genom, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China

[3] Zhengzhou Univ, Green Catalysis Ctr, Zhengzhou 450001, Henan, Peoples R China

[4] Zhengzhou Univ, Coll Chem, Zhengzhou 450001, Henan, Peoples R China

[5] Chongqing Univ, Sch Chem & Chem Engn, Chongqing 400030, Peoples R China

[6] Chongqing Univ, Chongqing Key Lab Theoret & Computat Chem, Chongqing 400030, Peoples R China

[7] Peking Univ, Key Lab Bioorgan Chem & Mol Engn, Minist Educ, Beijing 100871, Peoples R China

[8] Peking Univ, Beijing Natl Lab Mol, Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[9] Shenzhen Bay Lab, Shenzhen 518055, Peoples R China

来源：

ORGANIC LETTERS | 2021年 / 23卷 / 09期

基金：

美国国家科学基金会;

关键词：

CYCLOSPORINE-A; PEPTIDE CONFORMATIONS; CRYSTAL-STRUCTURE; CYCLOPHILIN; HISTORY; DISCOVERY;

D O I：

10.1021/acs.orglett.1c00881

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The non-immune-suppressive cyclophilin inhibitor CRV431 is a clinical candidate to cure nonalcoholic steatohepatitis (NASH) and has the potential to treat liver fibrosis and cancer incidence. Herein we report a concise chemical semisynthesis of CRV431 in four steps from the commercially available cyclosporine, featuring in this the flow-chemistry-based methylenation an intermolecular ring-closing metathesis and a Rh-catalyzed diastereoselective hydrogenation.

引用

页码：3421 / 3425

页数：5

共 30 条

[1] Apolipoprotein E controls cerebrovascular integrity via cyclophilin A [J].

Bell, Robert D. ;

Winkler, Ethan A. ;

Singh, Itender ;

Sagare, Abhay P. ;

Deane, Rashid ;

Wu, Zhenhua ;

Holtzman, David M. ;

Betsholtz, Christer ;

Armulik, Annika ;

Sallstrom, Jan ;

Berk, Bradford C. ;

Zlokovic, Berislav V. .

NATURE, 2012, 485 (7399) :512-516

[2] Emerging Trends in Flow Chemistry and Applications to the Pharmaceutical Industry [J].

Bogdan, Andrew R. ;

Dombrowski, Amanda W. .

JOURNAL OF MEDICINAL CHEMISTRY, 2019, 62 (14) :6422-6468

[3]

Borel JF, 2002, WIEN KLIN WOCHENSCHR, V114, P433

[4]

BOREL JF, 1989, PHARMACOL REV, V41, P239

[5] Extracellular cyclophilins in health and disease [J].

Bukrinsky, Michael .

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2015, 1850 (10) :2087-2095

[6] A general model for selectivity in olefin cross metathesis [J].

Chatterjee, AK ;

Choi, TL ;

Sanders, DP ;

Grubbs, RH .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (37) :11360-11370

[7] CYCLOSPORIN-A AND C NEW METABOLITES FROM TRICHODERMA-POLYSPORUM (LINK EX PERS) RIFAI [J].

DREYFUSS, M ;

HARRI, E ;

HOFMANN, H ;

KOBEL, H ;

PACHE, W ;

TSCHERTER, H .

EUROPEAN JOURNAL OF APPLIED MICROBIOLOGY, 1976, 3 (02) :125-133

[8]

FISCHER G, 1984, BIOMED BIOCHIM ACTA, V43, P1101

[9]

Frydrych C. S. V., 2012, U.S. Patent, Patent No. [20120088734A1, 20120088734]

[10] CYCLOPHILIN - A SPECIFIC CYTOSOLIC BINDING-PROTEIN FOR CYCLOSPORIN-A [J].

HANDSCHUMACHER, RE ;

HARDING, MW ;

RICE, J ;

DRUGGE, RJ .

SCIENCE, 1984, 226 (4674) :544-547

← 1 2 3 →