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

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.