Reaction SMILES: [C:1]([NH:8][C@H:9]([C:18]([OH:20])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[NH2:37][C@@H:38]([C:43]([O:45][CH3:46])=[O:44])[CH2:39][CH2:40][CH2:41][CH3:42]>CN(C)C=O>[C:1]([NH:8][C@H:9]([C:18]([NH:37][C@@H:38]([C:43]([O:45][CH3:46])=[O:44])[CH2:39][CH2:40][CH2:41][CH3:42])=[O:20])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O
Reactant: CCCC[C@@H](N)C(=O)OC
Agent: CC(C)COC(=O)Cl
Agent: Cl
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CCCC[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OC(C)(C)C)C(=O)OC
Temperature: -20 °C
Reaction time: 3 h

Procedure:
To a solution of 13.7 g of thionyl chloride in 100 ml of methanol at -20° C. is added 5 g of D-norleucine (Nle) with stirring. The reaction mixture is allowed to stand for 16 hours at room temperature. The methanol is removed under reduced pressure and the residue is shaken with diethyl ether to give a crystalline product, methyl D-norleucinate hydrochloride which is represented by the folowing formula ##STR53## A solution of 12.4 g of Boc-L-tyrosine in 100 ml of dimethylformamide is cooled to -20° C. and converted to a mixed anhydride by the addition of 1 equivalent of N-methyl morpholine and 1 equivalent of isobutylchloroformate. The reaction mixture is cooled to -30° C. and 4.48 ml of N-methylmorpholine is added followed by 6.65 g of methyl D-norleucinate hydrochloride. The reaction mixture is stirred 3 hours at room temperature and allowed to stand an additional 16 hours. The dimethylformamide is distilled off under high vacuum at 40° C., and the residue is shaken with ethyl acetate and water. The ethyl acetate fraction is separated and washed successively with 0.5 M potassium bisulfate solution, water, and 1 M potassium bicarbonate solution, then dried over magnesium sulfate. The solvent is removed under reduced pressure and the product is crystallized from 50 ml of isopropanol and 40 ml of water to give methyl Boc-L-tyrosyl-D-norleucinate. 4.06 Grams of methyl Boc-L-tyrosyl-D-norleucinate is suspended in 40 ml of 1 M potassium hydroxide solution and the mixture is stirred for one hour at room temperature. Excess 2 M potassium bisulfate solution is added and the product is taken up in ethyl acetate. The ethyl acetate solution is washed successively with 0.5 M potassium bisulfate solution and water then dried over magnesium sulfate. The solvent is removed under reduced pressure to give Boc-L-tyrosyl-D-norleucine. A solution of 1.42 g of Boc-L-tyrosyl-D-norleucine in 15 ml of tetrahydrofuran is cooled to -20° C. and converted to the mixed anhydride by the addition of 1 equivalent of N-methylmorpholine and 1 equivalent of isobutylchloroformate. To this reaction is added 1.24 g of methyl glycyl-L-phenylalanyl-3-amino-1-adamantanecarboxylate. The reaction mixture is stirred for 2 hours at room temperature then allowed to stand for 16 hours at room temperature. The reaction mixture is diluted with 200 ml of ethyl acetate and the ethyl acetate solution is washed successively with 0.5 M potassium bisulfate solution, water, and 1 M potassisum bicarbonate solution, then dried over magnesium sulfate. The solvent is removed under reduced pressure and the product is purified by low pressure chromatography on Woelm silica gel using a 100% chloroform to 5% methanol-95% chloroform gradient to give methyl Boc-L-tyrosyl-D-norleucyl-glycyl-L-phenylalanyl-3-amino-1-adamantanecarboxylate.