Study On Novel Protection And Deprotection Methods In Peptide Synthesis

Peptide and analogue are important and valuable drugs,such as thymopentin, L-Alanyl-L-Glutamine.The peptides play important roles in life science.In recent decades,a lot of biological activity peptides were found,so the higher demand was need in poly functional group peptide synthesis.Although many advances have been achieved,many methods are limited in chemoselective and atomic economy.The development of new methods for functional group protection and deprotection continues.This thesis focused on developing several novel,mild,chemoselective, green methods:Although currently there are a lot of methods available for amino and mercapto groups protection,only a few methods replace metal reduction of amine and mercapto functions.Removing a protecting group by treating a compound with a metal has huge applications in organic synthesis because of its simplity and the mild reaction conditions.We have found that magnesium tunings in acetic acid was a convenient way for deprotection of phenacyl N,S-protected amines and thiols.These magnesium turnings do not require activation before use,produce less acidic salts and generate less side products.Finally,this deprotection method can be performed in various organic solvents such as THF,acetone,showing that this method is widely applicable to the orthogonal organic synthesis bearing other kinds of fonctional groups.The above deprotection methodology was successfully incorporated into a short synthesis of Boc-(L)-Cys-Gly-OMe in high yield(88-95%).4-Picolyl group has proved to be efficient in the protection of carboxyl group in peptide synthesis.In addition,in peptide synthesis,4-picolyl group have been used as key intermediates to anchor the amino acid to the polymer support.The presence of this basic functional group also offers potential advantages for purification of products by electrophoresis or ion-exchange chromatography.In summary,a simple, efficient,and mild method for the cleavage of 4-picolyl group of protecting amino acid by treatment with magnesium in water in presence of other esters and sensitive protecting groups has been developed.3) A variety of natural polyphenols have become interesting and synthetic research directed at them has been carried out vigorously in recent years.The phenolic hydroxyl group(s) on them often plays an important role in their biological activity. Protection of the hydroxyl group(s) is necessary in order to maintain these activities and avoid expected side reactions.One of the most widely used protection groups for Phenolic hydroxyl groups has been the tert-butoxycarbonyl(Boc) group.Several methods for protecting hydroxyl were developed in presence of Lewis acid.We report a general selectively method for procedure for protecting phenols using COCl₂·6H₂O in the presence of a variety of other functional groups such as free hydroxyl group. This method is easy to perform and provides mild reaction conditions,excellent yield, and high chemo-selectivity procedure for protecting phenols in organic synthesis under CoCl₂·6H₂O.The addition,it was found that CuI could act the catlysis to proteced the alcohol group.These preliminary phenomena show that di-tert-butyldicarbonate(Boc₂O) are activated by Cu(â… ) and I(â… ).Deprotection of the Boc group,which is well known under acidic conditions,was also attempted using the same catalyst molecular iodine(30%) in acetonitrile. Preliminary experiments gave very satisfactory results.