Efficient access to all four stereoisomers of phenylalanine cyclopropane analogues by chiral HPLC

Bonded polysaccharide-derived chiral stationary phases were found to be useful for the preparation of the four stereoisomers of the cyclopropane analogue of phenylalanine (c(3)Phe) as well as for the direct determination of the enantiomeric purity of c(3)Phe derivatives by HPLC. Three chiral stationary phases, consisting of cellulose and amylose derivatives chemically bonded on allylsilica gel, were tested. The mixed 10-undecenoate/3, 5-dimethylphenylcarbamate of cellulose, 10-undecenoate/3, 5-dimethylphenylcarbamate of amylose and 10-undecenoate/p-methylbenzoate of cellulose were the starting polysaccharide derivatives for CSP-1, CSP-2, and CSP-3, respectively. Using mixtures of n-hexane/chloroform/2-propanol as mobile phase on a semi-preparative column (150 mm x 20 mm ID) containing CSP-2, we separated about 1.7 g of racemic cis-methyl 1-tert-butoxycarbonylamino-2-phenylcyclopropanecarboxylate (cis-6) and 1.2 g of racemic trans-methyl-1-tert-butoxycarbonylamino-2-phenylcycloprop-anecarboxyl ate (trans-6) by successive injections.