Synthesis of all four diastereoisomers of 4-(carboxymethyl)proline, a conformationally constrained analogue of 2-aminoadipic acid

Abstract
The dirhodium(II) tetraacetate catalysed reaction of ethyl diazoacetate with 2,3-dihydropyrrole-2,2-dicarboxylate 5 afforded the useful 2-azabicyclo[3.1.0]hexane derivative 6. Its conversion into the proline-γ-acetic acid equivalent 9 as well as into the four isomers constituting the 4-(carboxymethyl)proline 13(16a–19a) whose absolute configuration was established by an alternative asymmetric synthesis of two of them is described. Preliminary data concerning the affinity of compounds 16a–19a for the NMDA site of the NMDA receptor complex are also reported.

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