Prunusarmeniaca hydroxynitrile lyase (ParsHNL)-catalyzed asymmetric synthesis of cyanohydrins from sterically demanding aromatic aldehydes

Herein we report the biocatalytic asymmetric synthesis of cyanohydrins by using a new (R)-HNL from Prunusarmeniaca. Several sterically demanding aromatic aldehydes which have never been used as substrates for any known HNLs are employed for the new (R)-HNL from P. armeniaca. The cyanohydrins synthesized are obtained in good chemical yield with excellent enantioselectivities.

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(R)-(tert-Butyl-dimethyl-silanyloxy)-(4-pyrimidin-5-yl-phenyl)-acetonitrileC18H23N3OSiEe = 94%[α]D28=+26.4 (c 1.0, MeOH)Source of chirality: enzymatic hydrocyanationAbsolute configuration: (2R)

(R)-4-{4-[(tert-Butyl-dimethyl-silanyloxy)-cyano-methyl]-phenoxy}-benzonitrileC21H24N2O2SiEe = 96%[α]D28=+38.7 (c 1.0, MeOH)Source of chirality: enzymatic hydrocyanationAbsolute configuration: (2R)

(R)-(tert-Butyl-dimethyl-silanyloxy)-{3-[4-(tert-butyl-dimethylsilanyl)-piperazin-1-yl]-phenyl}-acetonitrileC24H43N3OSi2Ee = 94%[α]D28=+26.4 (c 1.0, MeOH)Source of chirality: enzymatic hydrocyanationAbsolute configuration: (2R)

(R)-2-Hydroxy-2-(3-phenoxy-phenyl)-acetonitrileC14H11NO2Ee = 99%[α]D28=+26.4 (c 1.0, MeOH)Source of chirality: enzymatic hydrocyanationAbsolute configuration: (2R)

(R)-(tert-Butyl-dimethyl-silanyloxy)-(6-methoxy-naphthalen-2-yl)-acetonitrileC19H25NO2SiEe = 97%[α]D28=+32.5 (c 1.0, MeOH)Source of chirality: enzymatic hydrocyanationAbsolute configuration: (2R)

(R)-Biphenyl-4-yl-(tert-butyl-dimethyl-silanyloxy)-acetonitrileC20H25NOSiEe = 96%[α]D28=+18.9 (c 1.0, MeOH)Source of chirality: enzymatic hydrocyanationAbsolute configuration: (2R)

(R)-(tert-Butyl-dimethyl-silanyloxy)-(4-methoxy-naphthalen-2-yl)-acetonitrileC19H25NO2SiEe = 94%[α]D28=+61.2 (c 1.0, MeOH)Source of chirality: enzymatic hydrocyanationAbsolute configuration: (2R)

(R)-(tert-Butyl-dimethyl-silanyloxy)-{4-[6-(tert-butyl-dimethylsilanyloxymethyl)-pyridin-2-yl]-phenyl}-acetonitrileC26H40N2O2Si2Ee = 98%[α]D28=+49.8 (c 1.0, MeOH)Source of chirality: enzymatic hydrocyanationAbsolute configuration: (2R)

(R)-(tert-Butyl-dimethyl-silanyloxy)-(4-pyridin-4-yl-phenyl)-acetonitrileC19H24N2OSiEe = 96%[α]D28=+23.45 (c 1.0, MeOH)Source of chirality: enzymatic hydrocyanationAbsolute configuration: (2R)