Thymopentin methyl ester conjugate and preparation method thereof

[0036] Chemical Synthesis of Intermediate Z-FPSDM-Arg(Pbf)-Lys(BOC)-OH

[0037] Z-FPSDM-Arg(Pbf)-Lys(BOC)-OMe was dissolved in MeOH (18ml), and LiOH aqueous solution (1.0M, 2.0ml) was added with stirring. The reaction solution was stirred at room temperature for 3 h until TLC showed that the reaction was complete. The solvent was pumped out under reduced pressure at 30°C, the residue was dissolved in DCM (60ml), and then washed with HCl solution (0.2M, 2×20ml) and saturated brine (2×20ml) successively, anhydrous Na 2 SO 4 After drying, the solvent was removed under reduced pressure at 30°C, and the resulting residue was washed with DCM / Et 2 O / Haxane (1:6:1) recrystallized to obtain the target product Z-FPSDM-Arg(Pbf)-Lys(BOC)-OH(MF.C 66 h 108 N 10 o 20 S, MW.1393.70).

[0039] Chemical Synthesis of FPSDM-TP-5 Derivatives

[0040] Z-FPSDM-Arg(Pbf)-Lys(BOC)-OH 197.6mg(MF.C 66 h 108 N 10 o 20 S, MW.1393.70, 0.142mmol) and HOCt 89.2mg (0.568mmol, 4eq) were dissolved in anhydrous DCM (10ml), and DIC 26μl (0.17mmol, 1.2eq) was added under stirring, and after stirring at room temperature for 1h, dropwise To the tripeptide derivative H-Asp(OtBu)-Val-Tyr-OMe0.066g (C 23 h 35 N 3 o 7 , MW.465.55, 0.142mmol) in DCM (8ml) solution, DIEA 0.10ml was added at the same time, stirred at room temperature for 8h until TLC showed that the reaction was complete. DCM (50ml) was added to the reaction solution, followed by HCl (0.2M, 2 × 20ml), H 2 O (20ml), NaOH (0.2M, 2×20ml) and saturated NaCl solution (2×20ml) were washed, then washed with Na 2 SO 4 Dry, and remove the solvent under reduced pressure at 30°C to obtain 0.188g of the crude product of the coupled compound Z-FPSDM-Arg(Pbf)-Lys(BOC)-Asp(OtBu)-Val-Tyr-OMe(MF.C 89 h 141 N 13 o 26 S, MW.184...

[0042] Synthesis of Boc-protected dipeptide derivatives

[0043] Boc-Val-OH (1-2, MW.217.27, 1.0864g, 5.0mmol) and HOCt (MF.C 5 h 7 N 3 o 3 , MW.157.12, 0.9427g, 6.0mmol, 1.2eq) was dissolved in anhydrous DCM (4.0ml), and DIC (MF.C 7 h 14 N 2 , MW.126.20, d.0.839, 0.91ml, 6.0mmol, 1.2eq) in the above solution. Suspend H-Tyr-OMe·HCl (1-1, MW.231.68, 1.1584g, 5.0mmol) in DCM (5.0ml), add DIEA (MF.C 8 h 19 N, MW.129.24, d.0.728, 1.95ml, 11.0mmol, 2.2eq), then the mixed solution of 1-2 / HOCt / DIC / DCM was added dropwise thereto, stirred at room temperature for 2h, and TLC detected that the reaction was complete. The reaction solution was filtered with NaHCO 3 (0.2M, 2×25ml), hydrochloric acid (0.2M, 2×20ml) and saturated brine (30ml) were extracted sequentially, anhydrous Na 2 SO 4 After drying and concentrating under reduced pressure, a light yellow oil was obtained, which was added with Et 2 O has urea precipitation, filter it quickly, add an appropriate amount of Et 2...