Synthesis of enantiomerically pure cis- and trans-cyclopentane analogues of phenylalanine

For the first time, all stereoisomers of 1-amino-2-phenylcyclopentanecarboxylic acid-c5Phe-have been synthesised. A Strecker reaction on 2-phenylcyclopentanone and further transformations of each amino nitrile into the amino acid provides cis-c5Phe and trans-c5Phe with high efficiency. A divergent synthetic route was then developed to obtain the target compounds cis- and trans-c5Phe in their racemic form. The preparation of the final enantiomerically pure amino acids and their corresponding N-protected derivatives was also achieved by HPLC resolution of one of the intermediates using a cellulose-derived chiral stationary phase. The relative stereochemistry of each amino acid and its precursors have been unambiguously assigned.