An Efficient Chemomicrobiological Synthesis of Stable Isotope-Labeled L-Tyrosine and L-Phenylalanine

Article abstract of DOI:10.1021/jo00358a004

L-Tyrosine specifically labeled with 2H, 13C, 18O, or 15N has been synthesized by using a combination of organic synthetic methods and the β-tyrosinase enzyme activity of the bacterium Erwinia herbicola.The following L-tyrosine isotopomers were prepared: L-<4'-13C>tyrosine from <1-13C>phenol and L-serine, L-<3',5'-13C2>tyrosine from <2,2-13C2>phenol and L-serine, L-<4'-18O>tyrosine from <18O>phenol and L-serine, L-<15N>tyrosine from <15N>ammonium sulfate, phenol, and pyruvate, and L-<2',3',5',6'-2H4>tyrosine from phenol and L-serine.The β-tyrosinase activitywas also used to prepare 2'-fluoro-L-tyrosine and 3'-fluoro-L-tyrosine from 3-fluorophenol and 2-fluorophenol, respectively.Phenol enriched with 13C was prepared by the condensation of <13C>acetone with nitromalonaldehyde, reduction of the resulting p-nitrophenol to p-aminophenol, and reductive removal of the nitrogen from the diazonium salt to form either <1-13C>- or <2,6-13C2>phenol in a 40percent overall yield from acetone.The yields of L-<13C>tyrosine were typically around 90percent from labeled phenol.Labeled L-phenylalanine was chemically prepared from L-tyrosine in a 75percent overall yield.This was deemed the best approach to labeled L-phenylalanine, given the efficient method for preparing L-tyrosine from phenol.The approach to labeled L-phenylalanine represents a unique combination of chemical synthesis (phenol), biosynthesis (L-tyrosine), and finally chemical synthesis (L-phenylalanine).The chirality is introduced by the biochemical step, obviating the need for elaborate and inherently inefficient chiral manipulations.