Liquid Phase Syntheses Of Peptide Aldehydesand Tripeptide-Rgd

Peptide aldehydes is a kind of inhibitor of many proteases in organism, It can adjust hemopoiesis and immunity, restraining the activeness of tumour; This kind of medicament had specific functional mechanism, which had important clinical value. Arg-Gly-Asp (RGD) was found by Yamada in fibronectin, which had the function of anti-blood platelets coagulates, repress tumor cell, promoting cell stick and attaching in material surface and so on. Summarized the synthesis and separate method of tripeptide, introduced the newest study of Peptide aldehydes. Depending on this basement, we studied the efficient synthesis method of high purity peptide aldehydes and RGD.In this study, we have synthesized eight compounds, namely Z-Ile-Glu(OtBu)-Ala- Leu-H, Fmoc-Phe-Val-H, Z-Val-Phe-H, AC-Leu-Leu-Ala-H, AC-Leu-Leu-(D)Ala-H, Z-Ala-Phe-H, Fmoc-Phe-Leu-H and Fmoc-Phe-Ala-H; all of them were depended on the methods of DCC coupling and Et3SiH reducing to peptide aldehydes. Choosing the fore compounds of Z-Ala-Phe-H and Fmoc-Phe-Ala-H as studying objects, we researched the influencing effects. The result indicated that Peptide aldehydes were obtained by Pd-C reducing from C-terminal S-benzyl ester modified peptide at geniality condition. First of all, the yield of Z-Ala-Phe-H and Fmoc-Phe-Ala-H were influenced indistinctively by quantity of Et3SiH; the yield of Z-Ala-Phe-H was improved by enhancing the quantity of Pd-C, but the yield of Fmoc-Phe-Ala-H was not affected conspicuously; expanding reaction time, the yield of Z-Ala-Phe-H was increased. During -25～75℃, the yield of Fmoc-Phe-Ala-H was not affected conspicuously by reactive temperature, but its yield was increased conspicuously during -55～-65℃. The merits of this synthetical method were as following: the synthetical process was simple, the reactive condition was mildness, and the yield was high. In addition, choosing benzyloxycarbonyl and nitryl as the protective group of arginine, C-terminal proactive benzyl easter asparagine as raw materials, we founded the shortest synthetical method of RGD, and all of the protective groups were removed only by one step of hydrogen sulfide.