Diverse pharmaceutical building blocks prepared with evolved enzymes

A panel of engineered enzymes can selectively oxidise a series of cyclic amines to form high-value pharmaceutical building blocks. The team used molecular dynamics studies to guide the enzyme evolution process and integrated this strategy into a concise drug synthesis.

Cyclic amines are a valuable motif in many pharmaceutical compounds and appear in around 60% of small-molecule drugs. There is consequently a huge demand for functionalised amines, but the inertness of C–H bonds makes the preparation of these fragments particularly challenging. ‘Without any other functional groups within these molecules, all of the chemistry happens at either the nitrogen atom or the adjacent C–H bonds,’ explains Jeremy Robertson, a synthetic organic chemist at the University of Oxford, UK. ‘We can’t normally access the other positions with chemical reagents.’