Synthesis of enantiopure 7-azanorbornane proline-α-amino acid chimeras by highly efficient HPLC resolution of a phenylalanine analogue

The enantiomerically pure conformationally constrained prolines, (1S,2S,4R)- and (1R,2R,4S)-2-phenyl-7-azabicyclo [2.2.1]heptane-1-carboxylic acid hydrochlorides, which are proline–phenylalanine chimeras, have been separately obtained by resolution of a key intermediate using chiral high performance liquid chromatography. The efficiency of the chromatographic resolution provides a general methodology for the preparation of both enantiomers of a broad variety of proline–α-amino acid chimeras with a 7-azanorbornane skeleton in enantiomerically pure form.This work was carried out with the financial support of Ministerio de Ciencia y Tecnologı́a and FEDER (project PPQ2001-1834). A. M. Gil would like to thank CSIC for an I3P grant.Peer reviewe