Synthesis of enantiopure l-(5-phenylfuran-2-yl)alanines by a sequential multienzyme process. Issue 18 (15th October 2015) - Bencze, László Csaba
Graphical abstract: Abstract: The enantioselective synthesis of unnatural amino acids is an attractive goal. Increasing attention has been given in recent years to the development of dynamic kinetic resolution processes, providing the desired enantiomer in almost quantitative yields and with high enantiopurity. Herein we describe an efficient sequential multi-enzyme process for the preparation of enantiopure 5-phenylfuran-2-ylalanines l -4a –d, starting from racemic 2-acetamido-3-(5-phenylfuran-2-yl)propanoic acids rac -1a –d . The first step, the CaL-B-mediated dynamic kinetic resolution of the racemic oxazolones provided the N - and C -protected l -amino acids l -2a –d (81–92% ee) with 100% theoretical yield. The protecting groups were removed in excellent yields by a second (mild non-stereoselective PLE mediated hydrolysis of the ester) and a third (Acylase I catalyzed stereoselective hydrolysis of the amide) enzymatic step, thus increasing the enantiomeric excess of the target compounds over 99%. Abstract : l -2-Amino-3-(5-phenylfuran-2-yl)propanoic acid: C13 H13 NO3 [ α ]D 25 = +28.2 ( c 1.0, CH3 COOH) ee >99% on Astec Chirobiotic-Tag HPLC column Source of chirality: Enzymatic resolution Absolute configuration: ( S ) Abstract : l -2-Amino-3-[5-(4-bromophenyl)furan-2-yl]propanoic acid: C13 H12 BrNO3 [ α ]D 25 = +10.8 ( c 1.0, CH3 COOH) ee >99% on Astec Chirobiotic-Tag HPLC column Source of chirality: Enzymatic resolution Absolute configuration: ( S ) Abstract : l -2-Amino-3-[5-(4-chlorophenyl)furan-2-yl]propanoic acid: C13 H12 ClNO3 [ α ]D 25 = +17.8 ( c 1.0, CH3 COOH) ee >99% on Astec Chirobiotic-Tag HPLC column Source of chirality: Enzymatic resolution Absolute configuration: ( S ) Abstract : l -2-Amino-3-[5-(2-chlorophenyl)furan-2-yl]propanoic acid: C13 H12 ClNO3 [ α ]D 25 = +16.7 ( c 1.0, CH3 COOH) ee >99% on Astec Chirobiotic-Tag HPLC column Source of chirality: Enzymatic resolution Absolute configuration: ( S )