Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation
Name
synthesis-of-emtricitabine-and-lamivudine-by-chlorotrimethylsilane-sodium-iodide-promoted-vorbruggen-glycosylation (1).pdf
Description
Submitted version
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589.6 KB
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Checksum (MD5)
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Author(s)
Mear, Sarah Jane
Nguyen, Long V.
Rochford, Ashley J.
Jamison, Timothy F.
Date Issued
January 2022
Journal
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.
Version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/acs.joc.1c02772
