New developments in the synthesis of pyrrolizidinone-based dipeptide isosteres

Abstract

1,3-Dipolar cycloaddition of acrylamide with the cyclic nitrone derived from proline tert-butyl ester has been employed in the synthesis of bicyclic Gly-( s- cis)Pro isosteres suitably protected for the Fmoc-based solid phase peptide synthesis. ( R)-1-Phenylethylamine was introduced as chiral auxiliary to resolve racemic intermediates and obtain enantiopure compounds. Using methacrylamide as dipolarophile, the analogous Ala-Pro mimetics have been prepared in racemic form, whereas the same strategy applied to methyl itaconate failed to give the corresponding Asp-Pro mimetic.