New enantiopure 7-azanorbornane β-substituted prolines by SN2 displacements at the Cγ of the side chain

Continuing our work on building new β-substituted prolines in enantiomerically pure form as new surrogates to be incorporated into model peptides, we describe functional group conversions and carbon–carbon bond forming reactions by SN2 displacements at the γ-position of the α-amino acid side chain of an azanorbornane derivative. This work extends efforts on the elaboration of the side arm at carbon C2 of the 7-azabicyclo[2.2.1]heptane core.

Figure optionsDownload as PowerPoint slide

Methyl (1S,2R,4R)-N-benzoyl-2-chloromethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC16H18ClNO3Ee = >98%[α]D25=-84.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,4R)

Methyl (1S,2R,4R)-N-benzoyl-2-bromomethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC16H18BrNO3Ee = >98%[α]D25=-92.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,4R)

Methyl (1S,2R,4R)-N-benzoyl-2-(4-methylphenyl)sulfonyloxymethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC23H25NO6SEe = >98%[α]D25=-6.7 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,4R)

Methyl (1S,2R,4R)-N-benzoyl-2-methylsulfonyloxymethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC17H21NO6SEe = >98%[α]D25=-32.4 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,4R)

Methyl (1S,2R,4R)-N-benzoyl-2-methyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC16H19NO3Ee = >98%[α]D25=-94.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,4R)

Methyl (1S,2R,4R)-N-benzoyl-2-methylthiomethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC17H21NO3SEe = >98%[α]D25=-90.0 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,4R)

Methyl (1S,2R,4R)-N-benzoyl-2-benzylthiomethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC23H25NO3SEe = >98%[α]D25=-75.1 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,4R)

Methyl (1S,2S,4R)-N-benzoyl-2-cyanomethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC17H18N2O3Ee = >98%[α]D25=-60.2 (c 0.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4R)

Methyl (1S,2S,4R)-N-benzoyl-2-azidomethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC16H18N4O3Ee = >98%[α]D25=-62.3 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4R)

Methyl (1S,2S,4R)-N-benzoyl-2-t-butoxycarbonylaminomethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC21H28N2O5Ee = >98%[α]D25=-68.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4R)

Methyl (1S,2S,4R)-N-benzoyl-2-(4,5-dimethoxycarbonyl-1,2,3-triazol-1-yl)methyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC22H24N4O7Ee = >98%[α]D25=-72.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4R)

Methyl(1S,2S,4R)-N-benzoyl-2-nitromethyl-7-azabicyclo[2.2.1]heptane-1-carboxylateC16H18N2O5Ee = >98%[α]D25=-34.0 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4R)

(1S,2R,4R)-2-Methyl-7-azabicyclo[2.2.1]heptane-1-carboxylic acid hydrochlorideC8H14ClNO2Ee = >98%[α]D25=-34.1 (c 0.4, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,4R)

(1S,2S,4R)-2-Carboxymethyl-7-azabicyclo[2.2.1]heptane-1-carboxylic acid hydrochlorideC9H14ClNO4Ee = >98%[α]D25=-25.5 (c 0.4, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4R)