Synthesis of d-camphor based γ-amino acid (1S,3R)-3-amino-2,2,3-trimethylcyclopentane carboxylic acid

Synthesis of a γ-amino acid derived from (1R,3S)-camphoric acid is described. d-(+)-Camphoric anhydride, prepared from d-(+)-camphoric acid by treatment with methanesulfonyl chloride and triethylamine, was reacted with benzyl alcohol and catalytic DMAP, and subsequently reacted in a Curtius rearrangement to afford the corresponding carbamate derivative. This derivative was converted to the desired γ-amino acid through hydrogenolysis.

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(1R,5S)-1,8,8-Trimethyl-3-oxabicyclo[3.2.1]octane-2,4-dione (d-camphoric acid)C10H15O3[α]D22=-0.9 (c 0.975, CHCl3)Source of chirality: (1R,5S)-camphoric acidAbsolute configuration: (1R,5S)

(1R,3S)-3-(Benzyloxycarbonyl)-1,2,2-trimethylcyclopentanecarboxylic acidC17H22O4[α]D22=+28 (c 1.00, CHCl3)Source of chirality: (1R,5S)-camphoric anhydrideAbsolute configuration: (1R,3S)

(1R,3S)-1,2,2-Trimethyl-3-((2-naphthylmethoxy)carbonyl)cyclopentane carboxylic acidC21H24O4[α]D22=+12 (c 0.976, CHCl3)Source of chirality: (1R,5S)-camphoric anhydrideAbsolute configuration: (1R,3S)

(1S,3R)-Benzyl 3-(benzyloxycarbonylamino)-2,2,3-trimethylcyclopentanecarboxylateC24H30NO4[α]D24=+0.2 (c 0.976, CHCl3)Source of chirality: (1R,5S)-camphoric anhydrideAbsolute configuration: (1S,3R)

Zwitterion of (1R,3S)-3-amino-2,2,3-trimethylcyclopentanecarboxylic acidC9H18NO2[α]D25=+51 (c 1.00, MeOH)Source of chirality: (1R,5S)-camphoric anhydrideAbsolute configuration: (1S,3R)