Study On Synthesis Of High-purity PEG-amine

Poly（ethylene glycol）（PEG） is a kind of chemical synthetic polyether.Amino functionalized PEG,that is,PEG-amine is an important derivative of PEG,is the key raw material for the synthesis of PEGylation drugs,but also widely used in organic chemistry,material chemistry,life science and other fields.At present,there are many synthesis methods of PEG-amine,but there are some shortcomings such as use of reagents or purification of the synthetic methods,it is difficult to obtain high-purity medicinal PEG-amine products.Therefore,it is very important to develop a simple and efficient preparation method of high-purity medicinal PEG derivatives for promoting the development of PEGylation drugs.In order to solve these problems,we developed a simple and efficient synthesis method to prepare high purity PEG-amine by using Di-tert-butyl iminodicarboxylate（Boc）₂NH as amination reagent.Using PEG as raw material,a simple and efficient method for the synthesis of PEG-amine derivatives was established through mesylate activation,（Boc）₂NH substitution and deprotection reaction.The effects of different alkaline conditions,solvent types,molar ratio of raw materials and temperature on the synthesis of PEG-amine protected by double Boc group were investigated.The results showed that the purity of the product was the highest when potassium tert-butanol as base,acetonitrile as solvent,3.0 times equivalent ammoniation reagent,and the reaction temperature at 60℃.Subsequently,structural characterization was carried out using ¹H NMR,¹³C NMR,GPC,and MALDI-TOF-MS,which showed purity greater than or equal to 95%and dispersion index less than or equal to 1.05.The method has wide applicability and can be used for the synthesis of single-ended amino functionalized PEG,double-ended amino functionalized PEG and multi-arm amino functionalized PEG,which lays a foundation for the further synthesis of PEGylation-amine derivatives.At last,this paper further synthesizes PEG with heterodox functional group by using the method found above.Including azide-PEG-amine（1k N₃-PEG-NH₂）,alkyne-PEG-amine（1k Alkyne-PEG-NH2）,carboxyl-PEG-amine（1k HOOCCH₃-PEG-NH₂·TFA）;And structural characterization was carried out through¹H NMR,¹³C NMR,and GPC.The target compounds showed high purity（≥95%）.This laid the material foundation for the application of the heterodox defunctive PEG-amine in the fields of material chemistry and life science.