Synthesis of novel N-protected β3-amino nitriles: study of their hydrolysis involving a nitrilase-catalyzed step

Several commercially available nitrilases were investigated with regard to their potential to hydrolyze N-protected β3-amino nitriles into their corresponding N-protected β3-amino acids.The biotransformations were obtained in different proportions depending on the nitrilase involved. The best hydrolysis results were achieved for the N-Cbz-β3-amino nitrile from l-alanine using the NIT-107, in a phosphate buffer at 0.05 M. However, no biotransformation into the corresponding acids was observed for the N-sulfonylamide β3-amino nitriles. Two simple and efficient procedures to prepare the β3-amino nitriles from their analogous α-amino acids are described. Thirty four new substances were synthesized and characterized over the course of this work.

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(S)-2-(4-tert-Butoxybenzyl)-1-(diphenylphosphoryl)aziridineC25H28NO2P[α]D20=-6.5 (c 5, CH2Cl2)Source of chirality: O-tert-butyl-l-tyrosineAbsolute configuration: (S)

(S)-N-(1-Hydroxypropan-2-yl)-4-nitrobenzenesulfonamideC9H12N2O5S[α]D20=-8.4 (c 1.0, MeOH)Source of chirality: l-alanineAbsolute configuration: (S)

(S)-N-(1-Hydroxy-3-methylbutan-2-yl)-4-nitrobenzenesulfonamideC11H16N2O5S[α]D20=+17.6 (c 1.0, MeOH)Source of chirality: l-valineAbsolute configuration: (S)

N-(2S)-1-Hydroxy-3-methylpentan-2-yl-4-nitrobenzenesulfonamideC12H18N2O5S[α]D20=+9.7 (c 1.0, MeOH)Source of chirality: l-isoleucineAbsolute configuration: (2S)

Benzyl (2R)-1-cyano-3-methylpentan-2-ylcarbamateC15H20N2O2[α]D20=-43.6 (c 1.0, MeOH)Source of chirality: l-isoleucineAbsolute configuration: (2R)

(S)-Benzyl 1-(4-tert-butoxyphenyl)-3-cyanopropan-2-ylcarbamateC22H26N2O3[α]D21=-3.1 (c 1.0, EtOH)Source of chirality: O-tert-butyl-l-tyrosineAbsolute configuration: (S)

(S)-Benzyl 1-(4-(benzyloxy)phenyl)-3-cyanopropan-2-ylcarbamateC25H24N2O3[α]D20=-6.4 (c 1.0, MeOH)Source of chirality: O-benzyl-l-tyrosineAbsolute configuration: (S)

tert-Butyl (2R)-1-cyano-3-methylpentan-2-ylcarbamateC12H22N2O2[α]D20=-4.5 (c 1.0, MeOH)Source of chirality: l-isoleucineAbsolute configuration: (2R)

N-((2R)-1-cyano-3-methylpentan-2-yl)-4-nitrobenzenesulfonamideC13H17N3O4S[α]D20=-46.9 (c 1.0, CHCl3)Source of chirality: l-isoleucineAbsolute configuration: (2R)

(S)-N-(1-Cyanopropan-2-yl)-P,P-diphenylphosphinic amideC16H17N2P[α]D23=+28.9 (c 3.6, CH2Cl2)Source of chirality: l-alanineAbsolute configuration: (S)

N-((2R)-1-Cyano-3-methylpentan-2-yl)-P,P-diphenylphosphinic amideC19H23N2OP[α]D20=-2.8 (c 2.8, CH2Cl2)Source of chirality: l-isoleucineAbsolute configuration: (2R)

(S)-N-(1-(4-tert-Butoxyphenyl)-3-cyanopropan-2-yl)-P,P-diphenylphosphinic amideC26H30O2N2P[α]D20=-27.8 (c 5, CH2Cl2)Source of chirality: O-tert-butyl-l-tyrosineAbsolute configuration: (S)

(S)-Benzyl 1-(4-(benzyloxy)phenyl)-3-hydroxypropan-2-ylcarbamateC24H25NO4[α]D24=-13.3 (c 0.33, CHCl3)Source of chirality: O-benzyl-l-tyrosineAbsolute configuration: (S)