Synthesis of optically active oxazoles from phosphorylated 2H-azirines and N-protected amino acids or peptides

A simple synthesis of optically active phosphorylated oxazoles 8, 10, 11, and 12 containing amino acid residues from 2H-azirine-phosphine oxides 1 or -phosphonates 6 is described. Ring-opening reaction of 2H-azirines derived from phosphine oxides 1 and phosphonates 6 with N-protected amino acids 2 gives functionalized phosphorylated ketamides 3 and 7. Cyclization of ketamides 3 and 7 with triphenylphosphine and hexachloroethane in the presence of triethylamine leads to the formation of racemic and optically active phosphorylated oxazoles containing N-protected amino acid residues 8 and 10. Deprotection of these oxazoles gives aminoalkyl oxazoles 11 and 12. 2H-Azirines 1 and 6 also react with N-protected peptides 13 and give functionalized ketamides 14 and 15, ring closure of which leads to the formation of phosphorylated oxazoles containing peptide residues 16 and 17. (C) 2002 Elsevier Science Ltd. All rights reserved.