Large-scale stereoselective synthesis of 1,3-oxathiolane nucleoside, lamivudine, via zrcl4 mediated n glycosylation

Jayashree, BS and Shenoy, Gautham G (2020) Large-scale stereoselective synthesis of 1,3-oxathiolane nucleoside, lamivudine, via zrcl4 mediated n glycosylation. Organic Process Research & Development, 24. pp. 387-397. ISSN 1083-6160

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Lamivudine (3TC); N-glycosylation; stereoselectivity; ZrCl4.
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Chemistry
Depositing User: KMC Library
Date Deposited: 15 Oct 2020 04:08
Last Modified: 15 Oct 2020 04:08
URI: http://eprints.manipal.edu/id/eprint/155850

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