- Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane-Sodium Iodide-Promoted Vorbrüggen Glycosylation
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By simple combination of water and sodium iodide (NaI) with chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl-NaI in wet solvent (0.1 M water)
- Mear, Sarah Jane,Nguyen, Long V.,Rochford, Ashley J.,Jamison, Timothy F.
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supporting information
p. 2887 - 2897
(2022/02/07)
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- Large-Scale Stereoselective Synthesis of 1,3-Oxathiolane Nucleoside, Lamivudine, via ZrCl4-Mediated N-Glycosylation
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A stereoselective large-scale synthetic process is described to produce 1,3-oxathiolane nucleoside, lamivudine. A mild, inexpensive, and readily available zirconium (IV) chloride (ZrCl4) catalyst acts as a substrate activator for the key N-glycosylation step at room temperature. An optimum of 0.5 equiv of ZrCl4 is required, which gives encouraging results with respect to chemical efficiency and stereoselectivity. The focus of this work was to develop a new Lewis acid catalyst for N-glycosylation reaction that permits mild and selective synthesis of lamivudine at a large scale. It allowed preferential formation of a single isomer of nucleoside out of four possible stereoisomers, starting from the corresponding 1,3-oxathiolane acetate substrate (racemic and/or diastereomeric mixture of isomers). The thermal behavior for the critical N-glycosylation step was also studied by differential scanning calorimetry and reaction calorimetry techniques.
- Aher, Umesh P.,Jadhav, Harishchandra S.,Jayashree, B. S.,Shenoy, Gautham G.,Singh, Girij P.,Srivastava, Dhananjai
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p. 387 - 397
(2020/04/08)
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- Semi-continuous multi-step synthesis of lamivudine
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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.
- Mandala, Devender,Chada, Sravanthi,Watts, Paul
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p. 3444 - 3454
(2017/04/26)
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- PROCESS FOR PRODUCING LAMIVUDINE AND EMTRICITABINE
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This invention provides for flow and batch synthesis processes for the production of Lamivudine and Emtricitabine, including flow and batch synthesis processes wherein at least of the synthesis steps are conducted in a solvent free environment.
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Page/Page column 15; 16; 17; 18
(2018/01/20)
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- COMBINED TREATMENT WITH A TLR7 AGONIST AND AN HBV CAPSID ASSEMBLY INHIBITOR
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The present invention is directed to compositions and methods for treating hepatitis B virus infection. In particular, the present invention is directed to a combination therapy comprising administration of a TLR7 agonist and an HBV capsid assembly inhibi
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Page/Page column 43; 44; 45
(2016/10/04)
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- COMPOUNDS FOR USE IN THE TREATMENT OF INFECTIOUS DISEASES
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The present invention relates to compounds of formula (I), wherein R1, R2, R3, R4, R5 and R6 are as described herein, and their prodrugs or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
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Page/Page column 33
(2016/05/02)
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- Highly stereoselective synthesis of lamivudine (3TC) and emtricitabine (FTC) by a novel N -glycosidation procedure
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The combined use of silanes (Et3SiH or PMHS) and I2 as novel N-glycosidation reagents for the synthesis of bioactive oxathiolane nucleosides 3TC and FTC is reported. Both systems (working as anhydrous HI sources) were devised to act as substrate activators and N-glycosidation promoters. Excellent results in terms of chemical efficiency and stereoselectivity of the reactions were obtained; surprisingly, the nature of the protective group at the N4 position of (fluoro)cytosine additionally influenced the stereochemical reaction outcome.
- Caso, Maria Federica,Dalonzo, Daniele,Derrico, Stefano,Palumbo, Giovanni,Guaragna, Annalisa
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supporting information
p. 2626 - 2629
(2015/06/16)
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- A STEREOSELECTIVE PROCESS FOR PREPARATION OF 1,3-OXATHIOLANE NUCLEOSIDES
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The present invention relates to a stereoselective glycosylation for the preparation of 1,3-oxathiolane nucleoside in high yield and high optical purity. The invention specifically relates to a process of the preparation of Lamivudine and Emtricitabine using zirconium (IV) chloride (ZrCl4) as a catalyst in glycosylation.
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Page/Page column 18; 19
(2013/03/26)
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- IMPROVED PROCESS FOR NUCLEOSIDES
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The present invention relates to improved process for the preparation of lamivudine or emtricitabine. Thus, (1'R,2'S,5'R)-menthyl- 5(R,S)-acetoxy-[1,3]-oxathiolane-2(R)-carboxylate is reacted with N-propinoyl cytosine in hexamethyl disilazane and then added trityl perchlorate to obtain a solid containing (1'R,2'S,5'R)-menthyl-5S-(N-4''-propionylcytosin-1''-yl)-[1,3]-oxathiolane -2R-carboxylate. The solid obtained above is reacted with methane sulfonic acid to obtain (2R,5S)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)- [1,3]-oxathiolane-2-carboxylic acid, 2S-isopropyl-5R-methyl-1R-cyclohexyl ester. The above compound is reduced with sodium borohydride to obtain lamivudine.
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Page/Page column 11-12
(2011/08/03)
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- PROCESS FOR PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE
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The present invention relates to a novel and stereoselective synthetic process for the preparation of optically active cis-nucleoside derivatives of compound of Formula (I), wherein R3 represents H, F, Cl, C1-16 alkyl.
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Page/Page column 8-9
(2011/11/30)
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- PROCESS FOR THE PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE
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The present invention relates to a novel and stereoselective synthetic process for the preparation of optically active cis-nucleoside derivatives of compound of Formula (I), wherein R3 represents H, F, Cl, C1-16 alkyl.
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Page/Page column 19-20
(2010/08/08)
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- Practical enantioselective synthesis of lamivudine (3TC) via a dynamic kinetic resolution
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A practical enantioselective synthesis of lamivudine 1 is described. A highly effective dynamic kinetic resolution of the 5-hydroxyoxathiolane, followed by chlorination and introduction of cytosine provides an efficient synthesis of lamivudine.
- Goodyear, Michael D.,Hill, Malcolm L.,West, Jono P.,Whitehead, Andrew J.
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p. 8535 - 8538
(2007/10/03)
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- Processes for the diastereoselective separation of nucleoside analogue synthetic intermediates
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The present invention relates to highly diastereoselective processes for production of cis-nucleosides and nucleoside analogues and derivatives in high optical purity and intermediates useful in those processes.
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