Pyrazines on solid support from peptides by periodinane oxidation of threonine side-chains. A quantitative chemical transformation (QCT) for combinatorial chemistry

The 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 TV-terminal amino acid afforded 3,6-dihydro-III-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).