Evaluation of Several Routes to Advanced Pregabalin Intermediates: Synthesis and Enantioselective Enzymatic Reduction Using Ene-Reductases

This publication describes the evaluation of four synthetic routes to the advanced pregabalin (Lyrica) intermediate 7 . Asymmetric reduction of ( E )- 7 with an ene-reductase (OPR1 from Lycopersicon esculentum ) gave a saturated cyanoester intermediate 5 with the desired S stereocenter in >99% ee. OPR1 also catalyzed the reduction of ( Z )- 7 to ( S )- 5, but with lower conversion and selectivity.