Chemical Synthesis Of Eptifibatide-a Platelet Glycoprotein Ⅱb/Ⅲa Receptor Antagonist

This thesis consists of two different routes about liquid phase peptide synthesis of Eptifibatide.In the part of route one, The process of preparing Cbz protected anino acid was optimized. Cbz protected anino acid was emplored to synthesize peptide derivatives and a few dipeptide, tripeptide and hexapeptide derivatives were synthesized with high yield, which take the advantage that Cbz could be easily removed by hydrogenation. On the other hand, a convenient and efficient method was established to synthesize lysine derivatives.α-NH2,ε-NH2 andα-COOH single protected lysine derivatives which were prepared using this method could be useful building blocks for peptide synthesis.In the part of route two, the synthesis and property of Fmoc protected anino acid was emplored and an effective method that could remove Fmoc group readily was establised. Fmoc protected anino acid was chosen as building block in Eptifibatid synthesis. Cysteine amide was prepared under very mild conditions by EEDQ, which provided a useful method in synthesizing amino acid amide. EEDQ was also proved to be an efficient coupling agent in amino acid couling with high yield and convenience. The effectivity of coupling agent DIC/HOCt was further proved during the coupling of tetrapeptide fragment and tripeptide fragment.An efficient method of forming intramolecular disulfide bond selectively while avoiding intermolecular side reaction was explored and establised after the aimed heptapeptide derivative was obtained. Several different conditions that could revove Boc and Tert-Butyl groups were tested and compared, and an Eptifibatide analog was obtained. Thiourea S-trioxide and S-ethylthiourea were employed to convert the amino group of the Eptifibatide analog into guanidino group, and finally Eptifibatide was obtained in mild and non-toxic conditions.