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

Bonded polysaccharide-derived chiral stationary phases were found to be use ful for the preparation of the four stereoisomers of the cyclopropane analo gue of phenylalanine (c(3)Phe) as well as for the direct determination of t he enantiomeric purity of c(3)Phe derivatives by HPLC. Three chiral station ary phases, consisting of cellulose and amylose derivatives chemically bond ed on allylsilica gel, were tested. The mixed 10-undecenoate/3,5-dimethylph enylcarbamate of cellulose, 10-undecenoate/3,5-dimethylphenylcarbamate of a mylose and 10-undecenoate/p-methylbenzoate of cellulose were the starting p olysaccharide derivatives for CSP-1, CSP-2, and CSP-3, respectively. Using mixtures of n-hexane/chloroform/2-propanol as mobile phase on a semi-prepar ative column (150 mm x 20 mm ID) containing CSP-2, we separated about 1.7 g of racemic cis-methyl 1-tert-butoxycarbonylamino-2-phenylcyclopropanecarbo xylate(cis-6) and 1.2 g of racemic trans-methyl-1-tert-butoxycarbonylamino- 2-phenylcyclopropanecarboxylate (trans-6) by successive injections. (C) 199 9 Wiley-Liss, Inc.