Technical Research On Double Protection Of Amino Acid

With the further research on the biological action of amino acids,peptide,pritein and so on in life sciense,the structural design and synthesis of peptide as well as its derivative turned into the effective means to research their structure and function.And then the needs for structures and kinds of amino acid are more and more miscellaneous.The fields of amino acid become quite active.In order to avoid side reaction ,the amino which will lead to side reaction should be protect beforehand.So the primary question of peptide synthsis is how to protect amino.But another active groups exsist in the structure of amino acids such as carboxyl,thiohydroxy,carboxamide and so on.They will also lead to side reaction.In order to ensure the reaction successfully,not only the amino needs protection,but also other groups.Then the peptide synthesis will go along according to our desire.This way willnot only avoid side reaction,but also reduce the material wastage and simplify the process of puritication.The object of the paper is diprotection of amino acids which has process as follow: 1. H-Gln-OH →Z-Gln-OH→Z-Gln(Trt)-OH →Fmoc- Gln(Trt)-OHIn the preparation of Z-Gln-OH ,we found that the reaction could perform only with water as the solution. Water can not only make the reaction perform completely, but also reduce the cost and simplify the process.Do like this also benefit the environment. In the preparation of Z-Gln(Trt)-OH, we adopted ethyl acetate as solution. One side ,it makes the reaction perform fluently and decrease the cost.On the other hand, it makes the products be exacted from water easily and decrease the consumption . In the preparation of Fmoc- Gln(Trt)-OH, we adopted acetone as solution to increase the yield and reduce the cost.2.H-Cys.HCl → H-Cys(Acm)-OH → Boc-Cys(Acm)-OHIn the preparation of Acm, we let acetamide and polyoxymethylene melt together to react completely. It benefits the reaction , increase the yield and make it easily operated because no water exsist. In the preparation of H-Cys(Acm)-OH , we recycled the trifluoroacetic acid by the means of rectification. The recycled rate was improved to 85% to 90% and the cost was effectively decreased.3.H-Arg-OH → Z- Arg-OH → Z-Arg(Pbf)-OH (Z-Arg(Pmc)-OH ,Z-Arg(Mtr)-OH) → H-Arg(Pbf)-OH (H-Arg(Pmc)-OH ,H-Arg(Mtr)-OH) →Fmoc -Arg(Pbf)-OH (Fmoc -Arg(Pmc)-OH , Fmoc -Arg(Mtr)-OH)In the preparation of Pbf-Cl Pmc-Cl and Mtr-Cl, the reacted mixture was dropped into icy NaHC03 solution , which reduced hydrolysis. In the preparation of Z-Arg(Pbf)-CHA Z-Arg (Pmc)-CHA and Z-Arg (Mtr)-CHA, we add TEBA as transrorm phase catalyst, which not only makes the reaction performed fluently the time, but also reduces the time and the consumption of Pbf-Cl Pmc-Cland Mtr-Cl.In the research process of this paper,I firstly refered to many papers to find out the research circumstance ,and then selected the prior course to improve and develop.I not only improved the preparation of target production,but also some material of protection groups.And then I did a lot of experiments to increase the yield, reduce the cost,and make them easily operated.What I have done was to make them fit for industrial production.