ENANTIOSELECTIVE ACYLATION OF β-PHENYLALANINE ACID AND ITS DERIVATIVES CATALYZED BY PENICILLIN G ACYLASE FROM Alcaligenes faecalis

Abstract

This study developed a simple, efficient method for producing racemic β-phenylalanine acid (BPA) and its derivatives via the enantioselective acylation catalyzed by the penicillin G acylase from Alcaligenes faecalis (Af-PGA). When the reaction was run at 25°C and pH 10 in an aqueous medium containing phenylacetamide and BPA in a molar ratio of 2:1, 8 U/mL enzyme and 0.1 M BPA, the maximum BPA conversion efficiency at 40 min only reached 36.1%, which, however, increased to 42.9% as the pH value and the molar ratio of phenylacetamide to BPA were elevated to 11 and 3:1, respectively. Under the relatively optimum reaction conditions, the maximum conversion efficiencies of BPA derivatives all reached about 50% in a relatively short reaction time (45–90 min). The enantiomeric excess value of product (ee_p ) and enantiomeric excess value of substrate (ee_s ) were all above 98% and 95%, respectively. These results suggest that the method established in this study is practical, effective, and environmentally benign and may be applied to industrial production of enantiomerically pure BPA and its derivatives.

Keywords:

• β-phenylalanine acid
• Alcaligenes faecalis
• derivatives
• enantioselective acylation
• penicillin G acylase

ACKNOWLEDGMENTS

This study was supported by the Huai'an City Industrial Fund for Science and Technology Support Program (HAG2010020) and the Foundation of Key Disciplines of Shanghai.

Notes

^a Conversion—the maximum conversion efficiency of 1a–1f.

^b Time—the reaction time for achieving the maximum conversion efficiencies of 1a–1f.

^c Determined as a ratio of initial rates for accumulation of both reaction products.

^d Determined by chiral HPLC.