Straightforward synthesis of various chiral pyrimidines bearing a stereogenic center adjacent to the C-2 position, including C-terminal peptide isosteres

Abstract

The present study describes an efficient access to enantioenriched pyrimidines' derivatives from readily available Boc-AA-NH₂ and β-enaminones. This strategy allows the synthesis of a large variety of chiral pyrimidines (18 examples) with good yields from the chiral pool. In the case of peptide isosteres, this procedure proved to be highly stereoretentive and paves the way to the construction of C-terminal modified peptidomimetics as illustrated in the synthesis of two original pyrimidines containing pseudo-dipeptides.

Keywords: Carboxamide; Chiral pyrimidine derivatives; Heterocycle; Peptide isosteres; β-Enaminone.