Chemoenzymatic resolution of epimeric cis 3-carboxycyclopentylglycine derivatives

Epimeric 3-carboxycyclopentylglycines (+)-10/(-)-10 and (+)-11/(-)-11 were efficiently prepared by the way of a sequence of D\iels-Alder and retro-Claisen reactions. The synthesis incorporates a concise and inexpensive chemoenzymatic resolution of racemic compounds 4,5a, the N,O-protected derivatives of amino acids 10,11. Systematic screening with different enzymes and microorganisms was performed to select a very efficient catalyst for the separation of the racemic mixtures. The reaction conditions allowing deprotection of both ester and amino functions and to avoiding epimerization processes were studied. Enantiomers (i.e., (+)-10/(-)-10 and (+)-11/(-)-11) were obtained in high enantiopurity. The absolute configuration of all stereocenters was unequivocally assigned. (c) 2006 Elsevier Ltd. All rights reserved.