Solid Phase Synthesis Process Of α-L-Asp-Asp And α-L-Lys-Lys

The study showed that the amino acid, its analogs and the polymer have important pharmacological effects. In the same time, Aspartic acid or lysine peptide compounds have anti-tumor effects, Fmoc-solid phase synthesis method paves the way for the synthesis of amino acids, their analogues and the polymer. In this dissertation, α-L-Asp-Asp, and α-L-Lys-Lys were synthesized by Fmoc-solid phase synthesis method. Course of the study were as follows.The wang-resins and amino acid were added to10ml DMF solution at a molar ratio of1:4, and were stirred at room temperature for8hours, and the diprotected product Fmoc-Asp(OtBu)-Ala-resin, Fmoc-Lys(Boc)-Ala-resin, Fmoc-Asp(OtBu)-Asp(OtBu)-Ala-resin and Fmoc-Lys(Boc)-Lys(Boc)-Ala-resi n. In order to deprotect the amino-group, then we add10ml20%piperidine in DMF solution to the dual protection product, and obtained the products NH2-Asp(OtBu)-Ala-resin, NH2-Lys(Boc)-Ala-resin, NH2-Asp(OtBu)-Asp(OtBu)-Ala-resin and NH2-Lys(Boc)-Lys(Boc)-Ala-resin. In order to cut down the resin and deprotection of the carboxy-protecting, then add10ml95%TFA aqueous solution to the filtrate, and obtained the four compounds which is α-L-Asp-Ala, α-L-Lys-Ala, α-L-Ala-Asp-Asp and α-L-Ala-Lys-Lys, In the next step, which laid the foundation for further synthesis of α-L-Asp-Asp and α-L-Lys-Lys, and study of their bioactictivity.The products were isolated and purified by RP-HPLC, optimal chromatographic conditions are as follows:UV detection wavelength:250nm; flow rate:1mL/min; column temperature: room temperature. The sample was injected into the High performance liquid chromatography manually. The purity of the products more than98%. The compounds were identified and analyzed by MS-ESI mass spectrometer, the resulting molecular weight of the target product are the same as the theoretical values, and characterized by mass spectrometry, infrared spectroscopy and hydrogen nuclear magnetic resonance spectroscopy were applid to characterize their absolute structure. It noted that the advantages of the method are mild reaction conditions, simplified operational procedure and high yield. What we have done are the foundation of synthesis of the target product α-L-Asp-Asp and α-L-Lys-Lys.