147126-67-8

Upstream product

• 200396-19-6 (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 5-hydroxy-1,3-oxathiolane-2-carboxylate 
• 108-24-7 acetic anhydride 
• 2216-51-5 (-)-menthol 
• 15356-60-2 (1S,2R,5S)-(+)-menthol 
• 111969-64-3 L-menthyl glyoxylate monohydrate 
• 147126-62-3 (2R,5R)-5-hydroxy-1,3-oxathiolane-2-carboxylic acid (1R,2S,5R)-5-methyl-2-isopropylcyclohexyl ester 
• 1309459-32-2 5-hydroxy-[1,3]oxathiolane-2-carboxylic acid 2-isopropyl-5-methylcyclohexyl ester 
• 147027-43-8 (2R,5R)-5-Acetoxy-[1,3]oxathiolane-2-carboxylic acid 
• 440105-45-3 TRANS-5-ACETOXY-1,3-OXATHIOLANE-2-CARBOXYLIC-ACID 
• 1214906-07-6 (-)-menthol 

Relevant academic research and scientific papers

Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane-Sodium Iodide-Promoted Vorbrüggen Glycosylation

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)

Large-Scale Stereoselective Synthesis of 1,3-Oxathiolane Nucleoside, Lamivudine, via ZrCl4-Mediated N-Glycosylation

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.

Semi-continuous multi-step synthesis of lamivudine

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.

PROCESS FOR PRODUCING LAMIVUDINE AND EMTRICITABINE

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.

COMBINED TREATMENT WITH A TLR7 AGONIST AND AN HBV CAPSID ASSEMBLY INHIBITOR

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

COMPOUNDS FOR USE IN THE TREATMENT OF INFECTIOUS DISEASES

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.

Highly stereoselective synthesis of lamivudine (3TC) and emtricitabine (FTC) by a novel N -glycosidation procedure

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.

A STEREOSELECTIVE PROCESS FOR PREPARATION OF 1,3-OXATHIOLANE NUCLEOSIDES

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.

IMPROVED PROCESS FOR NUCLEOSIDES

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.

PROCESS FOR PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE

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.