An Enzymatic Method to Obtain Enantiopure 3‐Pyridyl and Substituted Phenyl Alanine

ABSTRACT Chiral phenylalanine derivatives are important raw materials and building blocks for the synthesis of peptides and drug molecules. Enantiomerically pure D/L‐3‐pyridyl‐ and phenylalanine has shown wide application potential in the synthesis of various drug intermediates. This article focuses on two synthetic routes from different feedstocks. The first approach is an Erlenmeyer–Plöchl route study using N‐acetylglycine as starting material, whereas the second is an alkylation route study using diethyl acetamidomalonate as starting material. The key step is the resolution of N‐acetamido‐alanine esters using different quantities of fairly inexpensive Protamex proteinase to obtain pure enantiomeric D/L‐3‐pyridyl‐ and substituted phenylalanine or its derivative, with the ee value and purity of all products exceeding 99%. The different chiral arylalanine derivatives that can be prepared using the above two methods have good versatility. In Erlenmeyer–Plöchl process, N‐acetylglycine is used as starting material. In alkylation process, diethyl acetamidomalonate is used as starting material. %ee and purity of all products were above 99%. The novel syhthetic route to diverse chiral arylalanine derivatives features have versatility. Low cost, simplicity, mildness, high efficiency.