Synthesis of Hydroxylated Pipecolic Acids and Conformationally Constrained Derivatives

The aim of this research work is the development of new methodologies for the synthesis of enantiopure mono- and dihydroxylated pipecolic acid derivatives. In particular, the work will be focus on several complementary approaches to the synthesis of 4-hydroxy-, 5-hydroxy- and 4,5-dihydroxypipecolic acids. Our approach will be based on the chemistry of lactam-derived enol phosphates developed in our lab, which we have recently shown to be suited to the preparation of enantiopure 4-hydroxypipecolic acids. Moreover, with in mind the introduction of further constraints in hydroxypipecolic acids, we focused on the introduction of a cyclopropane ring in the position 2,3 of these molecules, in order to obtain mono- and dihydroxy methanopipecolic acid derivatives as a new class of conformationally constrained amino acid analogues to be employed as conformational probes and in the discovery of new drugs.