Stereochemistry of terpene derivatives. Part 7: Novel rigidified amino acids from (+)-3-carene designed as chiral GABA analogues

Several novel cyclopropyl-rigidified γ- and δ-amino acids 3–4 have been prepared starting from monoterpene (+)-3-carene 2. These compounds are proposed as chiral analogues of γ-aminobutyric acid (GABA) 1 and are expected to be of interest as potential inhibitors of GABA receptors.

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(−)-Benzyl {[(1R,3S)-2,2-dimethyl-3-(2-oxopropyl)cyclopropyl]methyl}carbamateC17H23NO3Ee = 100%[α]D24=-25.3 (c 2.0, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,3S)

(+)-[(1S,3R)-3-({[(Benzyloxy)carbonyl]amino}methyl)-2,2-dimethylcyclopropyl]acetic acidC16H21NO4Ee = 100%[α]D24=+15.9 (c 0.5, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1S,3R)

(+)-[(1S,3R)-3-(Aminomethyl)-2,2-dimethylcyclopropyl]acetic acidC8H15NO2Ee = 100%[α]D20=+34.1 (c 2.0, MeOH)Source of chirality: (+)-3-careneAbsolute configuration: (1S,3R)

(+)-Methyl {(1R,3S)-3-[(acetamino)methyl]-2,2-dimethylcyclopropyl}acetateC11H19NO3Ee = 100%[α]D24=+20.2 (c 1.0, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,3S)

(+)-Methyl {(1R,3S)-3-[(acetyloxy)methyl]-2,2-dimethylcyclopropyl}acetateC11H18O4Ee = 100%[α]D24=+28.7 (c 2.0, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,3S)

(−)-Methyl [(1R,3S)-3-(hydroxymethyl)-2,2-dimethylcyclopropyl]acetateC11H18O4Ee = 100%[α]D24=-28.5 (c 1.5, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,3S)

(+)-(1S,3R)-3-(2-Methoxy-2-oxoethyl)-2,2-dimethylcyclopropanecarboxylic acidC9H14O4Ee = 100%[α]D23=+49.7 (c 1.3, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1S,3R)

(−)-Methyl [(1R,3S)-3-{[(benzyloxy)carbonyl]amino}-2,2-dimethylcyclopropyl]acetateC16H21NO4Ee = 100%[α]D24=-42.0 (c 1.45, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,3S)

(−)-[(1R,3S)-3-{[(Benzyloxy)carbonyl]amino}-2,2-dimethylcyclopropyl]acetic acidC15H19NO4Ee = 100%[α]D25=-42.4 (c 0.8, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,3S)

(−)-[(1R,3S)-3-Amino-2,2-dimethylcyclopropyl]acetic acidC7H13NO2Ee = 100%[α]D25=-20.1 (c 0.7, MeOH)Source of chirality: (+)-3-careneAbsolute configuration: (1R,3S)