(1S,2S,3R,4R)-3-Aminobicyclo[2.2.1]heptane-2-carboxylic acid;hydrochloride

Method for Separating β-Amino Acid Isomers with Bicyclo[2.2.1]Heptane or Heptene Skeletons

Török G, et al. Journal of Chromatography A, 1998, 797(1-2), 177-186.

Compounds that contain the bicyclo[2.2.1]heptane structure are highly useful in the synthesis of various natural compounds like prostanoids, alkaloids, and nucleosides. Bicyclo[2.2.1]heptane-based β-amino acids and their derivatives are commonly used as initial components for a range of heterocycles. For example, to explore their biological activities and reactions, a number of alicycle-fused 1,3-heterocycles were created from racemic mixtures of diendo- and diexo-3-aminobicyclo[2.2.1]heptane-2-carboxylic acids and diendo- and diexo-3-amino-5-bicyclo[2.2.1]heptene-2-carboxylic acids.
For the separation and identification of the enantiomers of bicyclic β-amino acids, reversed-phase high-performance liquid chromatographic techniques were developed. This enabled the separation of racemic diendo-(1S,2S,3R,4R and 1R,2R,3S,4S) and diexo-(1S,2R,3S,4R and 1R,2S,3R,4S)-3-amino-bicyclo[2.2.1]heptane-2-carboxylic acids, as well as racemic diendo-(1S,2S,3R,4R and 1R,2R,3S,4S) and diexo-(1S,2R,3S,4R and 1R,2S,3R,4S)-3-amino-5-bicyclo[2.2.1]heptene-2-carboxylic acids through two methods. The first involved separating diastereomers formed by precolumn derivatization using chiral derivatizing reagents like Marfey's reagent and 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate. The second method utilized direct separation by employing a Crownpak CR(+) chiral stationary phase.