Studies on Synthesis of a Cycloheptapeptide and Effects of Different Metal Ions on the Cyclization

Abstract A cyclic heptapeptide, c(Gly‐Ile‐Pro‐Tyr‐Ile‐Ala‐Ala), which was isolated and identified from Stellaria yumumensis French (M), was synthesized by solution method for the first time. Protected heptapeptide Z‐Gly‐Ile‐Pro‐Tyr‐Ile‐Ala‐Ala‐OBzl was synthesized with 3‐(diethoxy‐phosphoryloxy)‐l,2,3‐benzotriazin‐4(3 H )‐one (DEPBT) as a coupling reagent. After deprotection of benzyl and benzyloxycarbonyl groups, a free linear heptapeptide H‐Gly‐Ile‐Pro‐Tyr‐Ile‐Ala‐Ala‐OH was cyclized in DMF (2 × 10 −3 mol/L) in the presence of nine different metal ions, i. e ., Li + , Na + , K + , Cs + , Mg 2+ , Ca 2+ , Bai 2+ , Nr 2+ and Cr 5+ respectively, using DEPBT as a coupling reagent. Univalent metal ion Cs + enhanced both the cyclization yield and cyclization rate of H‐Gly‐De‐Pro‐Tyr‐Ile‐Ala‐AlaOH, while some bivalent metal ions, such as Mg 2+ , Ca 2+ and Ni 2+ decreased the yields of c (Gly‐Ile‐Pro‐Tyr‐De‐Ala‐Ala) drastically. Trivalent metal ion Cr 3+ even inhibited the cyclization reaction completely.