A macrocyclic thrombin inhibitor, cyclotheonamide B (1, R=Ac) was synt
hesized via a new approach: guanidination of the ornithine-containing
macrocyclic peptide (2). In comparison of various coupling reagents, p
entafluorophenyl diphenylphosphinate (FDPP) gave the macrocyclic pepti
de (2) in good yield, and the configuration of the amino acid residue
has been revealed to be important for the macrolactamization.