Synthesis
General procedure for the synthesis of (S)-2-Amino-3-cyclohexylpropionic acid and (R)-2-Amino-3-cyclohexylpropionic acid from 3-cyclohexylpropionic acid: pyridoxamine 4a (2.1 mg, 0.0050 mmol), 4-(naphthalen-1-yl)-2-oxo-butyric acid (1a) (22.8 mg, 0.10 mmol), 2,2-diphenylglycine 11 ( 22.7 mg, 0.10 mmol), CH3COOH (48.0 mg, 0.80 mmol), EtOH (0.40 mL), and H2O (0.10 mL) were stirred for 24 hours at 25 °C. Upon completion of the reaction, the mixture was transferred to a 25 mL aubergine flask and methanol (10 mL) was added to completely dissolve the solid, followed by silica gel (0.50 g). The solvent was removed under reduced pressure at 25 °C. The residue was purified by fast column chromatography (silica gel, eluent ratio EtOH/ethyl acetate/25-28% aqueous ammonia solution = 100:58:16) to afford amino acid 2a (22.0 mg, 96% yield, 83% ee) as a white solid. To determine the enantiomeric excess (ee) of 2a, the amino acid was first converted to the corresponding methyl ester by treatment with diazomethane in methanol at room temperature, and subsequently analyzed by HPLC (Chiralcel OD-H column, mobile phase n-hexane: isopropanol = 85:15, flow rate 1.0 mL/min). The enantiomeric excesses (ee) of the products 2b-1 and 2o, as well as the dr values of the products 2m-n, were determined by converting the amino acids to the corresponding N-benzoyl methyl esters by treatment with thionyl chloride in methanol, then reacting with benzoic anhydride, and finally analyzed by HPLC.
