Pyrazines on Solid Support from Peptides by Periodinane Oxidation of Threonine Side‐Chains. A Quantitative Chemical Transformation (QCT) for Combinatorial Chemistry

Abstract

AbstractThe β‐hydroxymethylene in threonine residues adjacent to an N‐terminal amino acid were subjected to oxidation effected by Dess‐Martin periodinane on solid support. Fmoc‐cleavage at the N‐terminal amino acid afforded 3,6‐dihydro‐1H‐pyrazin‐2‐one, which oxidized spontaneously to the 1H‐pyrazin‐2‐ones (3a–v). A variety of naturally occurring and synthetic α‐amino acids gave rise to a diverse subset of functionalized 1H‐pyrazin‐2‐ones. An amino functionality in the side‐chain of the N‐terminal amino acid residue allowed elongation by conventional solid phase peptide chemistry (5a–b). Furthermore, elongation of the side‐chain with Thr and a second amino acid followed by oxidation resulted in bis 1H‐pyrazin‐2‐ones in high yield (8).