One-Pot Synthesis of l-Arylalanines from Arylaldehydes

Significance

A highly enantioselective and efficient chemoenzymatic approach to both natural and unnatural l-arylalanines is presented. The reaction sequence starts from simple arylaldehydes. These are converted into cinnamates via Wittig reaction with (triphenyl-λ⁵-phosphaneylidene)ethyl acetate, carried out in water. Without purification, the pH is adjusted to 8 by adding ammonia. Added PLE (porcine liver esterase) then catalyzes the ester cleavage to the ammonium salt. After completion of this step, PAL (phenylalanine ammonia lyase) is added and the cinnamates are transformed into the corresponding arylalanines with excellent enantioselectivities. The overall yields are good to excellent, and the authors reason that due to the low substrate specificity of PAL several other arylalanines should be accessible through this methodology.