A large proportion of FDA-approved drugs contain a nitrogen heterocycle — with the most common being the six-membered aromatic pyridine and its saturated analogue, piperidine. Piperidines often exhibit physicochemical properties, such as solubility and lipophilicity, that afford them an improved pharmacokinetic profile compared with pyridines. Writing in Science, teams led by Hans Renata and Phil Baran describe their collaboration to combine chemo- and enzymatic synthesis to produce a variety of medicinally relevant piperidines.

They began by identifying conditions for site-selective enzymatic hydroxylation of both l-pipecolic acid (l-Pip) and piperidine-3-carboxylic acid (d-Nip) to access a range of disubstituted piperidines — each with one hydroxyl and one carboxyl substituent, in a variety of substitution patterns and relative stereochemistries. Following a routine Boc-protection of the amino group, they then turned their attention to downstream functionalization using radical cross-coupling methods.