An efficient new enzymatic method for the preparation of β-aryl-β-amino acid enantiomers

An efficient synthesis of β-aryl-β-amino acid enantiomers has been developed via the lipase-catalysed enantioselective hydrolysis of the corresponding racemic ethyl esters in an organic solvent. High enantioselectivities (E >100) were observed when the lipase PS-catalysed reactions were performed with H2O (0.5 equiv) in diisopropyl ether at 45 °C. The products could be easily separated and were obtained in good yields of ⩾40%.

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(S)-3-Amino-3-phenylpropanoic acidC9H11NO2Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=-8 (c 0.27, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)

(S)-3-Amino-3-phenylpropanoic acid hydrochlorideC9H12ClNO2Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=+4 (c 0.3, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)

(S)-3-Amino-3-(3-fluorophenyl)propanoic acidC9H10FNO2Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=-1.8 (c 0.38, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)

(S)-3-Amino-3-(3-fluorophenyl)propanoic acid hydrochlorideC9H11ClFNO2Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=+5.7 (c 0.31, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)

(S)-3-Amino-3-(3,5-dichlorophenyl)propanoic acidC9H9Cl2NO2Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=-5.5 (c 0.38, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)

(S)-3-Amino-3-(3,5-dichlorophenyl)propanoic acid hydrochlorideC9H11ClFNO2Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=+5.7 (c 0.34, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)

(S)-3-Amino-3-(3,4-dimethoxyphenyl)propanoic acidC11H15NO4Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=+1.3 (c 0.51, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)

(S)-3-Amino-3-(3,4-dimethoxyphenyl)propanoic acid hydrochlorideC11H16ClNO4Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=+7.2 (c 0.315, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)

(S)-3-Amino-3-benzo[1,3]dioxol-5-ylpropanoic acidC10H11NO4Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=+4 (c 0.3, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)

(S)-3-Amino-3-benzo[1,3]dioxol-5-ylpropanoic acid hydrochlorideC10H12ClNO4Ee >99% by GC on a Chirasil l-Val column after derivatization with CH2N2 and Ac2O[α]D25=+8.9 (c 0.33, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (3S)