Total synthesis of cyclotheonamide A

Abstract

The potent serine protease inhibitor cyclotheonamide A was prepared in a convergent strategy from D-phenylalanine (D-Phe), vinylogous L-tyrosine (L-Vty), L-diaminopropanoic acid (L-Dpr), L-proline (L-Pro), and a hydrory acid derivative of L-arginine. Macrocyclic ring closure between the D-Phe and the L-Vty residues was performed via the pentafluorophenyl ester, and the Dess-Martin periodinane was used for the oxidation of the hydroxyamide to the α-ketoarginine (L-Kar) residue