Semi-continuous multi-step synthesis of lamivudine

被引：21

作者：

Mandala, Devender ^{[1
]}

Chada, Sravanthi ^{[1
]}

Watts, Paul ^{[1
]}

机构：

[1] Nelson Mandela Metropolitan Univ, Univ Way, ZA-6031 Port Elizabeth, South Africa

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2017年 / 15卷 / 16期

关键词：

ACTIVE PHARMACEUTICAL INGREDIENTS; ENZYMATIC RESOLUTION; ANTI-HIV; AGENT; EMTRICITABINE; INHIBITORS; 3TC(TM); TOOL; 3TC;

D O I：

10.1039/c7ob00480j

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We report the first continuous flow synthesis of lamivudine, an antiretroviral drug used in the treatment of HIV/AIDS and hepatitis B. The key intermediate (5-acetoxy oxathiolane) was prepared by an integrated two step continuous flow process from L-menthyl glyoxalate hydrate in a single solvent, in 95% overall conversion. For the crucial glycosidation reaction, using pyridinium triflate as the novel catalyst, an improved conversion of 95% was obtained. The overall isolated yield of the desired isomer of lamivudine (40%) was improved in the flow synthesis compared to the batch process.

引用

收藏

页码：3444 / 3454

页数：11

相关论文

共 23 条

[1]

Access campaign medicins sans frontiers, 2014, UNT WEB ANT PRIC RED

[2] Aminolysis of Epoxides in a Microreactor System: A Continuous Flow Approach to β-Amino Alcohols [J].

Bedore, Matthew W. ;

Zaborenko, Nikolay ;

Jensen, Klavs F. ;

Jamison, Timothy F. .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2010, 14 (02) :432-440

[3] Safe generation and use of bromine azide under continuous flow conditions - selective 1,2-bromoazidation of olefins [J].

Cantillo, David ;

Gutmann, Bernhard ;

Kappe, C. Oliver .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2016, 14 (03) :853-857

[4] Highly Stereoselective Synthesis of Lamivudine (3TC) and Emtricitabine (FTC) by a Novel N-Glycosidation Procedure [J].

Caso, Maria Federica ;

D'Alonzo, Daniele ;

D'Errico, Stefano ;

Palumbo, Giovanni ;

Guaragna, Annalisa .

ORGANIC LETTERS, 2015, 17 (11) :2626-2629

[5]

Chu C.K., 1993, NUCLEOSIDES NUCLEOTI

[6] Inhibition of clinically relevant mutant variants of HIV-1 by quinazolinone non-nucleoside reverse transcriptase inhibitors [J].

Corbett, JW ;

Ko, SS ;

Rodgers, JD ;

Gearhart, LA ;

Magnus, NA ;

Bacheler, LT ;

Diamond, S ;

Jeffrey, S ;

Klabe, RM ;

Cordova, BC ;

Garber, S ;

Logue, K ;

Trainor, GL ;

Anderson, PS ;

Erickson-Viitanen, SK .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (10) :2019-2030

[7] ENZYMATIC RESOLUTION OF OXATHIOLANE INTERMEDIATES - AN ALTERNATIVE APPROACH TO THE ANTIVIRAL AGENT LAMIVUDINE (3TC(TM)) [J].

COUSINS, RPC ;

MAHMOUDIAN, M ;

YOUDS, PM .

TETRAHEDRON-ASYMMETRY, 1995, 6 (02) :393-396

[8] Developing Continuous-Flow Microreactors as Tools for Synthetic Chemists [J].

Geyer, Karolin ;

Gustafsson, Tomas ;

Seeberger, Peter H. .

SYNLETT, 2009, (15) :2382-2391

[9] Practical enantioselective synthesis of lamivudine (3TC™) via a dynamic kinetic resolution [J].

Goodyear, MD ;

Hill, ML ;

West, JP ;

Whitehead, AJ .

TETRAHEDRON LETTERS, 2005, 46 (49) :8535-8538

[10] Continuous-Flow TechnologyA Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients [J].

Gutmann, Bernhard ;

Cantillo, David ;

Kappe, C. Oliver .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2015, 54 (23) :6688-6728