Method for the Solid-Phase Synthesis of Cyclic Pentapeptides

摘要

A method for the synthesis of a cyclic ornithine-proline-D-cyclohexylalanine-tryptophan-arginine pentapeptide of Formula A;; wherein R1 and R2 are, independently, —H, or —C(O)R3 where R3 is —CH2Ph, —CH2CH2Ph, —CH═CHPh, —C(NHAC)CH2Ph;the method comprising the steps of;forming a linear proline-D-cyclohexylalanine-tryptophan-arginine-ornithine pentapeptide of Formula B, attached to a polymeric resin; ; wherein R1 is as for Formula A, RES indicates the polymeric resin, and P1 and P2 are protecting groups;cyclising the linear pentapeptide of Formula B to form a cyclic pentapeptide of Formula C, attached to the polymeric resin; ; ;cleaving the cyclic peptide of Formula C from the resin providing a cleaved cyclic pentapeptide having a free amine group of an ornithine residue;optionally substituting the free amine group of the ornithine residue of the cleaved cyclic peptide;removing the protecting groups P1 and P2, to provide the cyclic peptide of Formula A.