De Novo Synthetic Route to a Combinatorial Library of Peptidyl Nucleosides

Abstract

A stereoselective synthetic route has been developed for the combinatorial synthesis of a structurally unique class of C-4′ side chain modified peptide-linked nucleosides. The synthetic strategy and approach involves initial synthesis of a strategically functionalized amino butenolide template, utilizing L-serine as a chiral starting material. Subsequent transformation of the above lactone to C4′ aminoalkyl substituted nucleosides, followed by the peptidic coupling of the C4′ side chain amine with various amino acids completed the syntheses of the target peptidyl nucleosides. Employing the above route, and utilizing a combination of easily available nucleobases (4) and amino acids (6) as the two diversity elements, synthesis of a 24-member combinatorial library of the title peptide-linked nucleosides has been accomplished.