Synthesis Of Enkephalin C-Terminal Derivatives Using New Reverse Direction Solid Phase Peptide Synthesis Method

In this thesis, the transfer active ester condensation (TAEC) technology and the Fmoc solid phase peptide synthesis (SPPS) method are combined together to establish a new reverse direction solid phase peptide synthesis (RD-SPPS) method. The new RD-SPPS method was applied for the synthesis of a series of Enkephalin C-terminal derivatives, and shown the following features:it kept the advantages of both TAEC technology and Fmoc SPPS method; provided an efficient way to synthesize peptide C-terminal derivatives under solid phase synthetic condition, and had a good application outlooking in peptide synthesis field.Four types of work were done in this thesis:(1) Explore efficient method to synthesize a series of amino acid Fmoc hydrazides, which were a type of new amino acid derivative, and were used as base material in the new RD-SPPS method;(2) Combine the TAEC technology and the Fmoc SPPS method together efficiently, design and establish a new RD-SPPS method, make this new method keep the advantages of both TAEC technology and Fmoc SPPS method, and can be used for the peptide C-terminal derivative synthesis under solid phase synthetic condition easily;(3) By exploring, comparing and optimation the reaction conditions systemically, the new RD-SPPS was established successfully;(4) The established new RD-SPPS method was used for the synthesis of a series of Enkephalin C-terminal derivatives and related intermediates, and the synthetic products were identified with mass spectrum and HPLC.