ol8b01872_si_001.pdf (1.22 MB)
Synthesis of (S)‑3-Amino-4-(difluoromethylenyl)-cyclopent-1-ene-1-carboxylic Acid (OV329), a Potent Inactivator of γ‑Aminobutyric Acid Aminotransferase
journal contribution
posted on 2018-07-13, 21:03 authored by Matthew
J. Moschitto, Richard B. Silverman(S)-3-Amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic
acid (OV329, 1) is being developed for the
treatment of epilepsy and addiction. The previous 14-step synthesis
of OV329 was low yielding, involved an unselective α-elimination
to form the cyclopentene, required the use of tert-butyllithium, and produced toxic selenium byproducts in the penultimate
step. A new synthesis, which avoids the aforementioned issues, was
carried out on large scale, reducing the step count from 14 to 9 steps
and increasing the overall yield from 3.7% to 8.1%.