| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1346851 | Tetrahedron: Asymmetry | 2015 | 7 Pages |
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%.
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l-2-Amino-3-(5-phenylfuran-2-yl)propanoic acidC13H13NO3[α]D25 = +28.2 (c 1.0, CH3COOH)ee >99% on Astec Chirobiotic-Tag HPLC columnSource of chirality: Enzymatic resolutionAbsolute configuration: (S)
l-2-Amino-3-[5-(4-bromophenyl)furan-2-yl]propanoic acidC13H12BrNO3[α]D25 = +10.8 (c 1.0, CH3COOH)ee >99% on Astec Chirobiotic-Tag HPLC columnSource of chirality: Enzymatic resolutionAbsolute configuration: (S)
l-2-Amino-3-[5-(4-chlorophenyl)furan-2-yl]propanoic acidC13H12ClNO3[α]D25 = +17.8 (c 1.0, CH3COOH)ee >99% on Astec Chirobiotic-Tag HPLC columnSource of chirality: Enzymatic resolutionAbsolute configuration: (S)
l-2-Amino-3-[5-(2-chlorophenyl)furan-2-yl]propanoic acidC13H12ClNO3[α]D25 = +16.7 (c 1.0, CH3COOH)ee >99% on Astec Chirobiotic-Tag HPLC columnSource of chirality: Enzymatic resolutionAbsolute configuration: (S)
