- The chemical resolution of racemic CIS-2-hydroxymethyl-5-(Cytosine-1′-YL)-1,3-oxathiolane (BCH-189) - One direct method to obtain lamivudine as anti-HIV and anti-HBV agent
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Racemic cis-BCH-189 can be resolved to (-)-enantiomer (lamivudine) and (+)-enantiomer by esterification of cis-2-hydroxymethyl-5-(N′4-acetylcyto sine-1′-yl)-1,3-oxathiolane and (+)-menthyl chloroformate in CH3CN with pyridine as base. The two diastereomers of ester were seperated by recrystallization in methanol at 0°C. Lamivudine was obtained by deprotection of (-)-diastereomer with high yield.
- Li, Ji-zhen,Gao, Lian-xun,Ding, Meng-xian
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Read Online
- 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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Read Online
- An Economical Route to Lamivudine Featuring a Novel Strategy for Stereospecific Assembly
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An economical synthesis of lamivudine was developed by employing a new method to establish the stereochemistry about the heterocyclic oxathiolane ring. Toward this end, an inexpensive and readily accessible lactic acid derivative served the dual purpose of activating the carbohydrate's anomeric center for N-glycosylation and transferring stereochemical information to the substrate simultaneously. Both enantiomers of the lactic acid derivative are available, and either β-enantiomer in this challenging class of 2′-deoxynucleoside active pharmaceutical ingredients can be formed.
- Abdiaj, Irini,Ahmad, Saeed,Burns, Justina M.,Gopalsamuthiram, Vijayagopal,Gupton, B. Frank,Krack, Rudy,McQuade, D. Tyler,Nelson, Ryan C.,Snead, David R.,Stringham, Rodger W.
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Read Online
- 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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Read Online
- Synthesis of an Oxathiolane Drug Substance Intermediate Guided by Constraint-Driven Innovation
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A new route was developed for construction of the oxathiolane intermediate used in the synthesis of lamivudine (3TC) and emtricitabine (FTC). We developed the presented route by constraining ourselves to low-cost, widely available starting materials - we refer to this as supply-centered synthesis. Sulfenyl chloride chemistry was used to construct the framework for the oxathiolane from acyclic precursors. This bond construction choice enabled the use of chloroacetic acid, vinyl acetate, sodium thiosulfate, and water to produce the oxathiolane.
- Burns, Justina M.,Gupton, B. Frank,Kashinath, K.,McQuade, D. Tyler,Snead, David R.,Stringham, Rodger W.
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Read Online
- 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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p. 2887 - 2897
(2022/02/07)
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- Nucleoside analogs of lamivudine preparation method (by machine translation)
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The invention relates to a method for the preparation of nucleoside analogs lamivudine. Specific, comprises the following steps: methanol in the solvent, a compound of formula III with a reducing agent, after treatment then outputs II compound, further purification, free, formula I compounds. This method is simple in operation, the resulting high product yield, purity as high as 99.5%. The method of post-processing process is simple, solvent is recycled for future use, in accordance with the needs of industrial production. (by machine translation)
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Paragraph 0039; 0040; 0044; 0045
(2019/07/11)
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- Asymmetric synthesis method of lamivudine
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The invention provides an asymmetric synthesis method of lamivudine. The synthesis method comprises: carrying out condensation on L-menthyl chloroformate used as a starting raw material and geminal dihaloethanol, hydrolyzing to obtain an acetaldehyde alcohol optically-active ester, carrying out condensation with 5,5-dihydroxy-1,4-dithiane to obtain trans 5-hydroxy-1,3-oxathiolane-2-methyl optically-active ester, acetylating, coupling with silanized cytosine, and finally removing the chiral auxiliary agent to obtain the product lamivudine. According to the present invention, the raw materials used in the entire synthesis process are cheap and readily available, and have high utilization rate, such that the synthesis cost of lamivudine is substantially reduced; the synthesis process is simple, the synthesis conditions are mild, the yield of the obtained lamivudine is high, the chiral substrate is easily removed during the synthesis, and the generated three-waste pollutants are less; andthe method is suitable for industrial large-scale production of lamivudine.
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Paragraph 0027; 0028; 0034; 0035; 0036
(2019/11/29)
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- A preparation method of lamivudine
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The invention discloses a method for preparation of lamivudine. Refined pure 5 S - (cytosine base - 1 ') - 1, 3 - oxathiolane - 2 - ethoxy carbonyl - (1' R, 2'S, 3' R) - menthyl ester; in the weak base and the solvent removed under the condition of chiral L - menthol to get a product of lamivudine. The material of the invention is cheap, the reagents used in the environmental protection, steps is relatively short, mild reaction conditions, atom utilization rate high, high yield, high chemical purity of the obtained product, reach the medical standard, suitable for large-scale production of lamivudine preparation method.
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Paragraph 0042; 0064; 0065
(2019/04/02)
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- Multienzymatic cascade synthesis of an enantiopure (2R,5R)-1,3-oxathiolane anti-HIV agent precursor
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An enantiopure (2R,5R)-1,3-oxathiolane was obtained using a multienzymatic cascade protocol. By employing a combination of surfactant-treated subtilisin Carlsberg and Candida antarctica lipase B, the absolute configuration of the resulting 1,3-oxathiolane ring was efficiently controlled, resulting in an excellent enantiomeric excess (>99%). This enantiopure 1,3-oxathiolane derivative is a key precursor to anti-HIV agents, such as lamivudine, through subsequent N-glycosylation.
- Ren, Yansong,Hu, Lei,Ramstr?m, Olof
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- Synthetic method for lamivudine
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The invention provides a synthetic method for lamivudine. The synthetic method comprises the following steps: cheap easily-available dihaloacetic acid is used as a raw material, the dihaloacetic acidand L-menthol are subjected to condensation, hydrolysis is performed to obtain menthyl glyoxylate, the menthyl glyoxylate and 2,5-dihydroxy-1,4-dithiane are subjected to condensation, halogenation isperformed, the halogenated product and silanized cytosine are subjected to coupling, reduction is performed, the reduced product and salicylic acid are subjected to salt formation to obtain the a salicylate, and finally recrystallization is performed to obtain the optically-pure lamivudine. According to the method provided by the invention, the raw materials used in the whole synthetic process arecheap and easy to obtain, the synthetic process is simple, the synthetic conditions are mild, so that the synthetic costs of the lamivudine are greatly reduced; the raw material utilization rate andreaction selectivity are high, so that the yield of the obtained lamivudine is higher; and at the same time, a chiral substrate is easily removed during the synthesis, three waste (waste water, wastegas and solid waste) generated in the method are less, and the method is suitable for industrialized large-scale production of the lamivudine.
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Paragraph 0028; 0036; 0038
(2019/11/21)
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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 22; 23; 24
(2018/01/20)
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- METHODS FOR THE TREATMENT OF HEPATITIS B AND HEPATITIS D VIRUS INFECTIONS
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It is disclosed a method for treating hepatitis B virus infection or hepatitis B virus/hepatits delta virus co-infection, the method comprising administering to a subject in need of such treatment a first pharmaceutically acceptable agent that comprises at least one phosphorothioated nucleic acid polymer and a second pharmaceutically acceptable agent that comprises at least one nucleoside/nucleotide analog HBV polymerase inhibitor.
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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 25; 26; 27
(2013/03/26)
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- AN IMPROVED PROCESS FOR THE MANUFACTURE OF LAMIVUDINE FORM I.
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The invention provides an improved process for the manufacture of Lamivudine Form I by adding a solution of Lamivudine in a mixture of water C1-4 alcohol into C3-8 ketone.
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Page/Page column 8
(2013/12/03)
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- Efficient asymmetric synthesis of lamivudine via enzymatic dynamic kinetic resolution
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The anti-HIV nucleoside lamivudine was asymmetrically synthesized in only three steps via a novel surfactant-treated subtilisin Carlsberg-catalyzed dynamic kinetic resolution protocol. The enantiomer of lamivudine could also be accessed using the same protocol catalyzed by Candida antarctica lipase B.
- Hu, Lei,Schaufelberger, Fredrik,Zhang, Yan,Ramstroem, Olof
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p. 10376 - 10378
(2013/10/22)
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- LAMIVUDINE OXALATE AND PREPARATION METHOD THEREOF
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Lamivudine oxalate, preparation method and crystalline forms thereof are disclosed. A preparation method of Lamivudine is also disclosed.
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Page/Page column 8
(2013/02/28)
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- LAMIVUDINE OXALATE AND PREPARATION METHOD THEREOF
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Lamivudine oxalate, preparation method and crystalline forms thereof are disclosed. A preparation method of Lamivudine is also disclosed.
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Paragraph 0071; 0072; 0073
(2013/03/26)
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- PROCESS FOR THE PREPARATION OF LAMIVUDINE AND NOVEL SALTS IN THE MANUFACTURE THEREOF
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The present invention relates to novel salts of Lamivudine and method for the preparation thereof. The present invention also relates to processes for the preparation of crystalline Lamivudine Form-I and Form-II from novel salts of Lamivudine.
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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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- NOVEL PROCESS FOR THE PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE
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The present invention relates to an improved process for the preparation of cis-nucleoside derivative of formula-1 involving chlorination of the compound of formula-2 followed by reaction with compound of formula-3 in presence of a base to get compound of formula-4, reacting the compound of formula-4 with an alkyl halide (RiX) to get a quaternary ammonium salt then with cytosine derivative of formula-5 to provide the compound of formula-6, optionally de-protecting the compound of formula-6 to the compound of formula-7, reducing compound of formula-7 with metal catalyst in presence of a buffer solution, then adding an organic acid to get the compound of formula-8, and converting the compound of formula-8 to cis-nucleoside derivative of formula-1. The present invention further relates to novel cis-nucleoside derivative of formula-8. The present invention also relates to a pharmaceutical composition comprising cis-nucleoside derivative of formula-1 with excipients.
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- AN IMPROVED PROCESS FOR THE MANUFACTURE OF LAMIVUDINE
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The present invention relates to an improved process for the Manufacture of Lamivudine. A process for the preparation of essentially enantiomerically pure (-)-[2R, 5S]-4-amino-1-[2- (hydroxymethyl)-1,3-oxathiolan-5-y1]-2(1H)-pyrimidin-2-one of formula (I), from L-menthyl glyoxylate is described. Also provided is a process for preparation of (+)-1- (2R/S-Cis)-4-amino-1-[(2-hydroxymethyl)-1,3-oxathiolan-5-y1]-2(1H)-pyrimidin-2-one of formula (XII), from L-menthyl glyoxylate.
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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 11-12
(2011/11/30)
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- PROCESS FOR THE MANUFACTURE OF CIS(-)-LAMIVUDINE
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An improved process for the manufacture of Lamivudine. The process involves: (a) resolution of racemic lamivudine (intermediate of formula IX) to cis (±) lamivudine of formula (XII) by forming a crystalline salt and separating the product from an organic solvent by fractional crystallization; (b) resolution of cis (±) lamivudine to cis (?) isomer involving formation of S-Binol adduct of formula XIV.
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- OPTICAL RESOLUTION OF SUBSTITUTED 1, 3-OXATHIOLANE NUCLEOSIDES
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Cis(±)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone is reacted with S(+)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate in methanol to obtain diastereomeric compounds. The diastereomeric compounds are subjected to selective crystallization to obtain (2R-Cis)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate. (2R-Cis)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate is treated with hydrochloric acid in water to obtain (2R-cis)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone.
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Page/Page column 5-6
(2011/10/13)
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- PREPARATION OF LAMIVUDINE FORM I
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A thermodynamically controlled process for preparing Form I polymorph of lamivudine is described, wherein the process involves crystallizing Form I at a temperature of from about 00C to about 500C from a mixture which comprises (a) lamivudine or an acid salt thereof or both, (b) a solvent system comprising water and at least one organic solvent, and optionally (c) Form I seed; wherein, when a lamivudine acid salt is employed in the mixture, the crystallizing step is conducted in the presence of a base; and wherein the water activity of the solvent system is maintained in a range in which Form I is thermodynamically the most stable form of lamivudine.
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Page/Page column 20-22
(2011/09/15)
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- OPTICAL RESOLUTION OF SUBSTITUTED 1.3-OXATHIOLANE NUCLEOSIDES
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Cis(±)- 4-Amino-1 -[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1 H)- pyrimidinone is reacted with S(+)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate in methanol to obtain diastereomeric compounds. The diastereomeric compounds are subjected to selective crystallization to obtain (2R-Cis)-4-Amino-1-[2- (hydroxymethyl)-i,3-oxathiolan-5-yl]-2(1 H)-pyrimidinone 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate. (2R-Cis)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5- yl]-2(1 H)-pyrimidinone 1,1 '-binaphthyl-2,2'-diyl hydrogen phosphate is treated with hydrochloric acid in water to obtain (2R-cis)-4-Amino-1-[2-(hydroxymethyl)- 1,3-oxathiolan-5-yl]-2(1 H)-pyrimidinone.
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Page/Page column 14
(2010/07/02)
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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 32
(2010/08/08)
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- A PROCESS FOR STEREOSELECTIVE SYNTHESIS OF LAMIVUDINE
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The present invention discloses a process for stereoselective synthesis of Lamivudine comprising the following steps: (a) performing a glycosylation reaction between the compound of formula (I) and cytosine or protected cytosine, and separating the reaction product by recrystallization to obtain the intermediate of formula (II); and (b) deprotecting the intermediate of formula (II) to obtain Lamivudine.
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Page/Page column 13
(2010/04/24)
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- PROCESS FOR THE PREPARATION OF LAMIVUDINE FORM I
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The present invention provides a process for preparing a stable crystalline solid of Lamivudine polymorphic Form I, which does not change to Form II during storage and pharmaceutical unit operations.
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Page/Page column 3
(2010/08/07)
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- PROCESS FOR THE PREPARATION OF SUBSTITUTED 1,3-OXATHIOLANES
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The present invention relates to a process for the preparation of substituted 1,3-oxathiolanes. The present invention specifically relates to a process for the preparation of lamivudine.
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Page/Page column 7-8
(2010/12/29)
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- CRYSTALLINE FORM I OF LAMIVUDINE AND ITS PREPARATION
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The present invention relates to a stable crystalline Form I of lamivudine. The present invention further relates to a process for the preparation of the stable crystalline Form (I) of the stable crystalline Form (I) of lamivudine.
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Page/Page column 3-4
(2010/12/31)
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- PROCESS FOR THE PREPARATION OF SUBSTITUTED 1,3-OXATHIOLANES
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The present invention relates to a process for the preparation of substituted 1,3- oxathiolanes. The present invention specifically relates to a process for the preparation of lamivudine.
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Page/Page column 17-18
(2009/07/03)
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- A novel method for large-scale synthesis of lamivudine through cocrystal formation of racemic lamivudine with (S)-(-)-1,1′-Bi(2-naphthol) [(S)-(BINOL)]
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A large-scale synthesis of (-)-[2R,5S]-4-amino-1- [2-(hydroxymethyl)- 1,3-oxathiolan-5-yl]-2(1H)-pyrimidin-2-one (lamivudine) through resolution of racemic lamivudine by cocrystal formation with (S)- BINOL has been demonstrated. Lamivudine of very high pu
- Roy, Bhairab Nath,Singh, Girij Pal,Srivastava, Dhananjai,Jadhav, Harishchandra S.,Saini, Manmeet B.,Aher, Umesh P.
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experimental part
p. 450 - 455
(2010/04/22)
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- AMORPHOUS LAMIVUDINE AND ITS PREPARATION
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The present invention relates to amorphous lamivudine. The present invention further relates to a process for the preparation of amorphous lamivudine by spray drying.
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Page/Page column 6
(2009/07/03)
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- PROCESS AND INTERMEDIATES FOR THE PREPARATION OF SUBSTITUTED 1, 3-OXATHIOLANES, ESPECIALLY LAMIVUDINE
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The present invention relates to process and intermediates for the preparation of substituted 1,3-oxathiolanes. The present invention specifically relates to a process for the preparation of lamivudine.
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Page/Page column 24
(2009/07/03)
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- PROCESS FOR THE PREPARATION OF LAMIVUDINE FORM I
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The present invention provides a process for preparing a stable crystalline solid of Lamivudine polymorphic Form I, which does not change to Form II during storage and pharmaceutical unit operations.
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Page/Page column 7-8
(2009/04/25)
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- CRYSTALLINE FORM I OF LAMIVUDINE AND ITS PREPARATION
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The present invention relates to a stable crystalline Form I of lamivudine. The present invention further relates to a process for the preparation of the stable crystalline Form (I) of the stable crystalline Form (I) of lamivudine.
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Page/Page column 9-10
(2009/07/03)
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- METHOD FOR RESOLVING ENANTIOMERS FROM RACEMIC MIXTURE HAVING CHIRAL CARBON IN ALPHA POSITION OF NITROGEN
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Disclosed relates to a simplified method for resolving enantiomers by dissolving a racemic mixture having chiral carbon in α-position of nitrogen and an amino acid to prepare a diastereomeric salt, not using catalyses or enzymes, with enhancing the optical purity remarkably. Moreover, the present invention can prepare the enantiomers in large quantities without using expensive catalysts or without controlling the reaction conditions for the activity of enzymes applied.
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Page/Page column 6-7
(2009/03/07)
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- METHOD FOR RESOLVING ENANTIOMERS FROM RACEMIC MIXTURE HAVING CHIRAL CARBON IN ALPHA POSITION OF NITROGEN
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Disclosed relates to a simplified method for resolving enantiomers by dissolving a racemic mixture having chiral carbon in α-position of nitrogen and an amino acid to prepare a diastereomeric salt, not using catalyses or enzymes, with enhancing the optical purity remarkably. Moreover, the present invention can prepare the enantiomers in large quantities without using expensive catalysts or without controlling the reaction conditions for the activity of enzymes applied.
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Page/Page column 17; 21
(2010/11/28)
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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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- PROCESS FOR PREPARING SUBSTITUTED 1,3-OXATHIOLANES WITH ANTIVIRAL PROPERTIES
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Disclosed are processes for preparing compounds of formula (I) and pharmaceutically acceptable salts or esters thereof, wherein R2 is a purine or pyrimidine base or an analogue or derivative thereof; and Z is S, S = O or SO2. The invention also relates to
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- 2-Substituted-4-substituted-1,3-dioxolanes and use thereof
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Nucleoside analogues containing a 1,3-dioxolane structure are suitable antiviral agents, particulary for the treatment of the HIV infections in mammals, especially humans. Examples of the nucleoside analogues include: cis-2-acetoxymethyl-4-(thymin-1′-yl)-1,3,-dioxolane, cis-2-hydroxymethyl-4-(thymin-1′-yl)-1,3-dioxolane, cis-2-benzoyloxymethyl-4-(cytosin-1′-yl)-1,3-dioxolane, and cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-dioxolane. These compounds can be in the form of their racemates or their separate enantiomers.
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Page column 39
(2010/11/29)
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- 1,3-oxathiolane nucleoside analogues
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(?)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one, its pharmaceutically acceptable derivatives, pharmaceutical formulation thereof, methods for its preparation and its uses as an antiviral agent are described.
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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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- Processes for the diastereoselective synthesis of nucleoside analogues
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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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- Processes for preparing substituted 1,3-oxathiolanes with antiviral properties
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Disclosed are processes for preparing compounds of the formula (I) and pharmaceutically acceptable salts or esters thereof: STR1 wherein R2 is a purine or pyrimidine base or an analogue or derivative thereof; and Z is S, S=O or SO2.
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- Enantioselective enzymatic synthesis of the anti-viral agent lamivudine (3TC)
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A novel enzymatic resolution of α-acetoxysulfides has been used as the key step in the synthesis of the important antiviral nucleoside analogue lamivudine. The synthesis proceeds via a configurationally stable hemithioacetal which cyclises in situ to form the required oxathiolane nucleus, which can then be converted into the target nucleoside in 4 steps.
- Milton,Brand,Jones,Rayner
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p. 6961 - 6964
(2007/10/02)
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