Synthesis of Enantiomerically Pure Ring-Substituted l-Pyridylalanines by Biocatalytic Hydroamination

Current routes to nitrogen-containing heteroarylalanines involve complex multistep synthesis and are often reliant on protection/deprotection steps and wasteful chromatographic purifications. In order to complement existing methodologies, a convenient telescopic strategy was developed for the synthesis of l-pyridylalanine analogues (12 examples) and other l-heteroarylalanines (5 examples) starting from the corresponding aldehydes. A phenylalanine ammonia lyase (PAL) from Anabaena variabilis was used as the biocatalyst to give conversions ranging between 88 and 95%, isolated yields of 32–60%, and perfect enantiopurity (>99% ee) by employing an additional deracemization cascade where necessary.