Reaction SMILES: [NH2:1][C@@H:2]([C:6]([NH:8][C@H:9]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])[CH:3]([CH3:5])[CH3:4].CC1C=CC(S(O)(=O)=O)=CC=1.[NH:35]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[C@H:36]([C:38](O)=[O:39])[CH3:37].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C([O-])(O)=O.[Na+]>ClCCl.O>[NH:35]([C:41]([O:43][C:44]([CH3:45])([CH3:47])[CH3:46])=[O:42])[C@H:36]([C:38]([NH:1][C@@H:2]([C:6]([NH:8][C@H:9]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:10][CH:11]([CH3:12])[CH3:13])=[O:7])[CH:3]([CH3:5])[CH3:4])=[O:39])[CH3:37]
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: CC(C)C[C@H](NC(=O)[C@H](N)C(C)C)C(=O)OCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: ClCCl
Solvent: O
Product: CC(C)C[C@H](NC(=O)[C@H](NC(=O)[C@H](C)NC(=O)OC(C)(C)C)C(C)C)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of DVal-Leu-OBzl.p-TsOH(375 mg, prepared in Example(1-a)), Boc-Ala(144 mg), HOBT.H2O (122 mg) and N-methylmorpholine(84 μl) in dichloromethane (1.6 ml) was added EDCI.HCl(153 mg) under ice cooling. The reaction mixture was stirred at room temperature for 2 h and saturated NaHCO3 was added. The mixture was extracted with dichloromethane(15 ml×3). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by dry column flash chromatography on silica gel(Merck, KIESELGEL 60) with chloroform/methanol(50/1) for elution to give Boc-Ala-DVal-Leu-OBzl(306 mg) as a colorless powder. The powder(300 mg) was added by portions to TFA(1.2 ml) under ice cooling and the reaction mixture was stirred at the same temperature for 30 min. TFA was removed in vacuo. Saturated NaHCO3 (2 ml) was added to the residue and the mixture was extracted with dichloromethane(15 ml×3). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure to give Ala-DVal-Leu-OBzl(233 mg) as a colorless powder. To a solution of the tripeptide(157 mg), Boc-DCys(O3Na)(117 mg) and HOBT.H2O(67 mg) in DMF(0.8 ml) was added EDCI.HCl (84 mg) under ice cooling. The reaction mixture was stirred at room temperature for 20 h and concentrated in vacuo. To the residue was added saturated NaHCO3 (2 ml) and the mixture was extracted with EtOAc(20 ml×3). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by dry column flash chromatography on silica gel(Merck, KIESELGEL 60) with dichloromethane/methanol(10/1) for elution to give Boc-DCys(O,Na)-Ala-DVal-Leu-OBzl(210 mg) as a colorless powder. The powder(100 mg) was added by portions to TFA (0.75 ml) under ice cooling and the mixture was stirred under ice cooling for 1 h. TFA was removed in vacuo. To the residue was added 1N NaOH(0.15 ml) and the mixture was concentrated in vacuo to give crude DCys(O3Na) -Ala-DVal-Leu-OBzl(108 mg) which was used without further purification in the next step. To a solution of the crude tetrapeptide(108 mg), Z-DTrp(51 mg) and HOBT.H2O (25 ml) in DMF(0.3 ml) was added EDCI.HCl(32 mg) under ice cooling. The reaction mixture was stirred at room temperature for 2 h and concentrated in vacuo. To the residue was added saturated NaHCO3 (1 ml) and the mixture was extracted with EtOAc(10 ml×3). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by dry column flash chromatography on silica gel (Merck, KIESELGEL 60) with dichloromethane/methanol (10/1) for elution to give Z-DTrp-DCys(O3Na) -Ala-DVal-Leu-OBzl(110 mg) as a colorless powder. The powder(97 mg) was dissolved in DMF(0.55 ml) and 10% Pd/C (29 mg) was added. The resulting mixture was stirred vigorously at room temperature under an atmosphere of hydrogen(under atmospheric pressure) for 3 h, and filtered. The filtrate was concentrated in vacuo to give DTrp-DCys(O3Na)-Ala-DVal-Leu(63 mg) as a colorless powder. A solution of the pentapeptide(33 mg) in DMF (2.5 ml) was added dropwise to a solution of HOBT.H2O (12 mg) and EDCI HCl(14 mg) in DMF(2.5 ml) over a period of 1.5 h. The reaction mixture was stirred at room temperature for 2 h and concentrated in vacuo. The residue was purified by reverse-phase column chromatography(NACALAI TESQUE, COSMOSIL 75 C18 -OPN) with methanol/water(4/1) for elution to give the title compound(17 mg) as a colorless powder.