High Efficient and Green Approach to the Synthesis of Leuprolide in Continuous-flow Microreactor

被引：3

作者：

Li, Shijie ^{[1
]}

Yang, Yang ^{[1
]}

Cui, Yingying ^{[1
]}

Su, Xianbin ^{[1
]}

机构：

[1] Nanjing Tech Univ, Coll Chem Engn, Nanjing 210009, Peoples R China

来源：

CHEMICAL JOURNAL OF CHINESE UNIVERSITIES-CHINESE | 2020年 / 41卷 / 07期

关键词：

Microchannel reactor; Leuprorelin; Continuous-flow; Liquid phase synthesis; PHASE PEPTIDE-SYNTHESIS;

D O I：

10.7503/cjcu20200032

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A high efficient and green approach was repored for the synthesis of leuprorelin which is a nonapeptide analogue of gonadotrophin releasing hormone (GnRH) used to treat a wide range of sex hormone-related disorders-based on a continuous-flow system. Benzyloxycarbonyl(Cbz) -protected amino acids were used in this approach and coupling reaction was carried out in micro-channel reactors efficiently followed by extraction to remove impurities. A rapid and clean deprotection of Cbz then successfully achieved through hydrogenolysis via a column packed with Pd/C catalyst. This approach enabled the stiochiometric amidation of peptide chain elongation and catalytic deprotection hence the consumption of raw materials were dramatically reduced. This new strategy will find more application in peptide manufacturing.

引用

页码：1559 / 1566

页数：8

共 35 条

[1] On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system [J].

Adamo, Andrea ;

Beingessner, Rachel L. ;

Behnam, Mohsen ;

Chen, Jie ;

Jamison, Timothy F. ;

Jensen, Klavs F. ;

Monbaliu, Jean-Christophe M. ;

Myerson, Allan S. ;

Revalor, Eve M. ;

Snead, David R. ;

Stelzer, Torsten ;

Weeranoppanant, Nopphon ;

Wong, Shin Yee ;

Zhang, Ping .

SCIENCE, 2016, 352 (6281) :61-67

[2] Liquid-Phase Synthesis of Bridged Peptides Using Olefin Metathesis of a Protected Peptide with a Long Aliphatic Chain Anchor [J].

Aihara, Keisuke ;

Komiya, Chiaki ;

Shigenaga, Akira ;

Inokuma, Tsubasa ;

Takahashi, Daisuke ;

Otaka, Akira .

ORGANIC LETTERS, 2015, 17 (03) :696-699

[3]

Audubert C., 2017, ANGEW CHEM, V129, P6391

[4] Continuous flow hydrogenations using novel catalytic static mixers inside a tubular reactor [J].

Avril, A. ;

Hornung, C. H. ;

Urban, A. ;

Fraser, D. ;

Horne, M. ;

Veder, J-P ;

Tsanaktsidis, J. ;

Rodopoulos, T. ;

Henry, C. ;

Gunasegaram, D. R. .

REACTION CHEMISTRY & ENGINEERING, 2017, 2 (02) :180-188

[5] Environmentally benign peptide synthesis using liquid-assisted ball-milling: application to the synthesis of Leu-enkephalin [J].

Bonnamour, Julien ;

Metro, Thomas-Xavier ;

Martinez, Jean ;

Lamaty, Frederic .

GREEN CHEMISTRY, 2013, 15 (05) :1116-1120

[6]

Cen T, 2010, CHINESE J ORG CHEM, V30, P837

[7]

[程荡 Cheng Dang], 2019, [化工进展, Chemical Industry and Engineering Progress], V38, P556

[8] The expanding utility of continuous flow hydrogenation [J].

Cossar, Peter J. ;

Hizartzidis, Lacey ;

Simone, Michela I. ;

McCluskey, Adam ;

Gordon, Christopher P. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2015, 13 (26) :7119-7130

[9] A porous structured reactor for hydrogenation reactions [J].

Elias, Y. ;

von Rohr, Ph. Rudolf ;

Bonrath, W. ;

Medlock, J. ;

Buss, Axel .

CHEMICAL ENGINEERING AND PROCESSING-PROCESS INTENSIFICATION, 2015, 95 :175-185

[10] Synthesis of Liraglutide Through Threonine Ligation [J].

Fan Jiahui ;

Bian Yanan ;

Su Xianbin .

CHEMICAL JOURNAL OF CHINESE UNIVERSITIES-CHINESE, 2018, 39 (12) :2679-2685

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