A new route was developed for construction of the oxathiolane intermediate used in the synthesis of lamivudine (3TC) and emtricitabine (FTC). We developed the presented route by constraining ourselves to low-cost, widely available starting materials-we refer to this as supply-centered synthesis. Sulfenyl chloride chemistry was used to construct the framework for the oxathiolane from acyclic precursors. This bond construction choice enabled the use of chloroacetic acid, vinyl acetate, sodium thiosulfate, and water to produce the oxathiolane.