op0c00145_si_001.pdf (1.74 MB)
Synthesis of an Oxathiolane Drug Substance Intermediate Guided by Constraint-Driven Innovation
journal contribution
posted on 2020-05-21, 16:42 authored by K. Kashinath, David R. Snead, Justina M. Burns, Rodger W. Stringham, B. Frank Gupton, D. Tyler McQuadeA 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 materialswe 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.