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

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Author(s)
Mear, Sarah Jane
•
Nguyen, Long V
•
Rochford, Ashley J
•
Jamison, Timothy F
Date Issued
January 14, 2022
Journal
The Journal of Organic Chemistry
Publisher
American Chemical Society (ACS)
Citation
Mear, Sarah Jane, Nguyen, Long V, Rochford, Ashley J and Jamison, Timothy F. 2022. "Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation." The Journal of Organic Chemistry.
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Original manuscript
Abstract
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) activates a 1,3-oxathiolanyl acetate donor for N-glycosylation of silylated cytosine derivatives, leading to cis-oxathiolane products with up to 95% yield and >20:1 dr. This telescoped sequence is followed by recrystallization and borohydride reduction, resulting in rapid synthesis of (±)-FTC/3TC from a tartrate diester.
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DOI of Published Version
10.1021/acs.joc.1c02772
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