The Resolution and Absolute Stereochemistry of the Enantiomers of<i>cis</i>-1-[2-(Hydroxymethyl)-1,3-oxathiolan-5-yl)cytosine (BCH189): Equipotent Anti-HIV Agents

Storer, Richard; Clemens, Ian R.; Lamont, Brian; Noble, Stewart A.; Williamson, Christopher; Belleau, B.

doi:10.1080/07328319308021208

Cited by 39 publications

(11 citation statements)

References 17 publications

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“…Storer et al (1993) reported the structure and absolute configuration of (2' R,5' S)-N 4-(4-bromobenzoyl)-1-(2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosirie, the 4-bromobenzoyl deriva- (Johnson, 1976) stereodiagram showing the molecular conformations of the two molecules in the asymmetric unit. The molecules shown illustrate the intermolecular base pairing hydrogen bonding.…”

Section: Resultsmentioning

confidence: 99%

Absolute Configuration of the Antiviral Agent (−)-cis-5-Fluoro-1-[2-Hydroxymethyl)-1,3-Oxathiolan-5-yl]Cytosine

Roey

Pangborn

Schinazi

et al. 1993

Antivir Chem Chemother

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The structure and absolute configuration of (−)- cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (FTC), has been determined by X-ray crystallographic analysis. The results confirm that the L-isomer of the nucleoside analogue is the most active enantiomer and that the correct absolute configuration of (−)-FTC is 5-fluoro-(2′R,5′S)-(−)-1-[2-hydroxymethyl)oxathiolan-5-yl]-fluorocytosine. The two molecules in the asymmetric unit show conformations that combine conformational features of two other classes of potent antiviral nucleosides. Both oxathiolane rings have the 3′-sulphur atom in nearly perfect S3′- exo envelope conformations, similar to what is observed for 3′-azido-3′-deoxythymidine (AZT) and 2′,3′-dideoxycytidine. One of the two molecules has a glycosylic link conformation in which the base is eclipsed with the C5′-O1′ bond. This mimics the high- anti conformation that has been observed in the structures of several 2′,3′-didehydro-2′,3′-dideoxypyrimidine nucleosides but is inaccessible for saturated pyrimidine nucleosides. However, the observed conformations cannot be superimposed adequately with other active antiviral nucleosides to suggest a common ‘active site’ conformation.

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Section: Resultsmentioning

confidence: 99%

Absolute Configuration of the Antiviral Agent (−)-cis-5-Fluoro-1-[2-Hydroxymethyl)-1,3-Oxathiolan-5-yl]Cytosine

Roey

Pangborn

Schinazi

et al. 1993

Antivir Chem Chemother

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“…In an alternative route, 5 0 -nucleotidase from snake venom was used to resolve lamivudine-5 0 -phosphate, requiring additional (enzymatic) dephosphorylation. 94 Final stage kinetic resolution of a racemic mixture of lamivudine using cytidine deaminase eliminated the need for its 5 0 -phosphate analogue. 95 The structurally related anti-viral agent, emtricitabine could be obtained in enantiopure form through pig liver esterase-catalysed resolution of its 5 0 -butanoate ester as shown by Schinazi and co-workers.…”

Section: Methodsmentioning

confidence: 99%

Biocatalytic routes to anti-viral agents and their synthetic intermediates

Slagman

Fessner

2021

Chem. Soc. Rev.

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“…As a permanent cure for HIV has remained elusive to date, efficient access to bulk quantities of lamivudine and emtricitabine is critical in developing countries, as increased demand is expected . Although there are several methods reported for the synthesis of lamivudine 1 and emtricitabine 2 as a single enantiomer, we required an efficient new route, which was suitable for the large‐scale synthesis, which ideally would facilitate the synthesis at a lower cost.…”

Section: Introductionmentioning

confidence: 99%

An Improved Synthesis of Lamivudine and Emtricitabine

Mandala

Watts

2017

ChemistrySelect

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An improved method was developed to prepare cis(‐)nucleosides, such as lamivudine (3TC) and emtricitabine (FTC). A solvent free reaction and catalyst free reaction was developed, with reduced reaction times to afford high yields in the preparation of the key 5‐hydroxy oxathiolane intermediate. For the acetylation, we developed a greener procedure using NaHCO3 as the base instead of pyridine. In addition, a new reagent namely pyridinium triflate, was used for the crucial N‐glycosidation reaction for the first time towards the synthesis of bioactive oxathiolane nucleosides 3TC and FTC.

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The Resolution and Absolute Stereochemistry of the Enantiomers ofcis-1-[2-(Hydroxymethyl)-1,3-oxathiolan-5-yl)cytosine (BCH189): Equipotent Anti-HIV Agents

Cited by 39 publications

References 17 publications

Absolute Configuration of the Antiviral Agent (−)-cis-5-Fluoro-1-[2-Hydroxymethyl)-1,3-Oxathiolan-5-yl]Cytosine

Absolute Configuration of the Antiviral Agent (−)-cis-5-Fluoro-1-[2-Hydroxymethyl)-1,3-Oxathiolan-5-yl]Cytosine

Biocatalytic routes to anti-viral agents and their synthetic intermediates

An Improved Synthesis of Lamivudine and Emtricitabine

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