The Synthesis Of Methoxy-poly(Ethyleneglycol) Derivatives

The methoxy polyethyleneglycol?mPEG?is broad-spectrum polyether polymer in the area of medicine,electron,chemical engineering and foodstuff.The protein drugs and enzymes,property of the insolubility,enzymolysis,etc,can be improved when the modifier bonds them.Because of the low-purity of mPEG derivatives which are prepared in modern technology,the high-purity of mPEG derivatives needs to be developed in new way urgently.In the shudy the NH2-mPEG₂₀₀₀,MAl-mPEG₂₀₀₀ and mPEG₂₀₀₀-iodoacetamide,mPEG₂₀₀₀-SS and mPEG₂₀₀₀-SC which were used to modify proteineous enzyme's carboxylic,sulfydryl and amino respectively were synthesized by mPEG₂₀₀₀.In totally,the three kinds of five species mPEG derivatives were synthesized.The reseash emphasized highest yield of intermediates and final products,obtained by optimized conditions of orthogonal experiment for derivatives intermediates and final product since most of them needed several reactions to complete.And the methods of testing the yield were selected by the property of the different end groups.The polyethylene glycol monomethyl ether p-toluene sulfonic acid ester(mPEG₂₀₀₀-OTs)was synthesized firstly in the progress of the synthsis of mPEG₂₀₀₀-NH2.The optimal reaction conditions of mPEG₂₀₀₀-OTs were obtained by the oryhogonal experiment as follow: reaction time was 12 h,mole ratio was n(mPEG₂₀₀₀): n?TsCl?=1: 5.5 and reaction temperature was 25?,the yield was 71.0 % by demonstration test.The amino polyethylene glycol monomethyl ether(mPEG₂₀₀₀-NH2)was synthesized by the mPEG₂₀₀₀-OTs?71.0%?in the way of high-pressure and the Gabriel.The mPEG₂₀₀₀-NH2 which was occupied by high-pressure needed less react-steps and more yield than the Gabrial.And its purity could reach to 50%.The novel method of synthesizing MAl-mPEG₂₀₀₀ had less react-step and more yield than recoding method of paper,and its purity could reach to 27.4%.In the progress of synthesizing mPEG₂₀₀₀-iodoacetamide,the optimal reaction conditions were obtained by the oryhogonal experiment as follow: reaction time was 6 h,n?aceticacid,2-iodo-,1,1'-anhydride?: n(mPEG₂₀₀₀-iodoacetamide)=5 and reaction temperature was30³5?,the yield was 59.1%% by demonstration test.The purity could reach to 41.4%.It was intermediate of CmPEG₂₀₀₀ belonged to mPEG₂₀₀₀-SS and mPEG₂₀₀₀-SC which used to modify animo group have difference in the synthsis method that leaded to larger gap in the yield.The intermediate of CmPEG₂₀₀₀ which used to synthsize mPEG₂₀₀₀-SC was oxidized by Jones regent.The yield of CmPEG₂₀₀₀ was 90%,and the purity could reach to 66.5%?In this paper,the three species of five kinds modifiers,used to modify enzymes was estimated systematically.It was preparation for mPEG derivatives that provides an important theoretical basis and technical support.