Structural features of N-benzylated-β-amino acid methyl esters essential for enantiodifferentiation by lipase B from Candida antarctica in hydrolytic reactions

Racemic N-benzylated-β2, β3, and β2,3-amino acid methyl esters were synthesized and submitted to hydrolysis catalyzed by lipase B from Candida antarctica in organic solvents. Good to excellent enantioselectivities were obtained for β3- and β2,3-amino acid derivatives, whereas the enzyme showed a poor stereoselectivity toward β2-amino acid derivatives.

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(R)-3-(Benzylamino)butanoic acidC11H15NO2Ee = 85%[α]D20 = −30.4 (c 1.1, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(S)-3-(Benzylamino)-3-phenylpropanoic acidC16H17NO2Ee >99%[α]D20 = −51.9 (c 1.1, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

(S)-3-(Benzylamino)-4,4-dimethylpropanoic acidC14H21NO2Ee >99%[α]D20 = +26.0 (c 0.3, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

3-(Benzylamino)-2-methylpropanoic acidC11H15NO2Ee = 12%[α]D20 = +1.5 (c 1.0, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

3-(Benzylamino)-2-phenylpropanoic acidC16H17NO2Ee = 6%[α]D20 = +1.5 (c 1.0, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

(2R,3R)-3-(Benzylamino)-2-methylbutanoic acidC12H17NO2Ee = 82%[α]D20 = −59.2 (c 1.0, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (2R,3R)

(2S,3R)-3-(Benzylamino)-2-methylbutanoic acidC12H17NO2Ee >99%[α]D20 = −21.6 (c 1.0, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (2S,3R)