Study On Protected Amino Acid Preparation

The solid phase peptide synthesis is control synthesis of different amino acids from the certain sequence. The difficulty is that the functional groups of amino acids are easy to react with peptide synthesis reagents ,which generate the increase of by-products and the low reaction efficiency. Therefore ,in solid phase peptide synthesis, the functional groups of amino acids should be temporarily protected, which can guarantee the favoring process of solid phase peptide synthesis.Firstly, the classification and characteristics of protected amino acids and protect ion groups were reviewed. Then the distinguishingly taking off conditions of protection groups, the generally introducing reaction process and the application of protected amino acids were expatiated.Based on the vast market foreground and the high synthesis costs, this paper focused on the synthesis methods of the materials of peptide synthesis-protected amino acids, optimized the synthesis condition and did some research on the amplificatory reaction and checked the raw material costs , so that could provide the high pure and lower costs protected amino acids for peptide synthesis.I Research on the protect synthesis of alkyl side chain amino acidsThis paper selected three kinds of alkyl side chain amino acids-L-Ala, L-Val and L-Phe to protect, and did the amplificatory reaction in 2L reactor. Passed the experiments to investigate many influent factors, such as temperature, time, the reaction system pH and the category of protection reagents. The best synthesis reaction temperature of protected Z-Ala, L-Val is 20℃, protected L-Phe is 25℃.The reaction time is respectively for 70min, 60min and 90min.The total productivity is respectively at 90%, 88% and 89%,which were all higher than the cultural reports. The purity of products were all higher than 98%.II Research on protect synthesis of amino acids contain side chain function groups This paper primarily selected L-Ser, L-Thr and L-Tyr which contain side chainhydroxyl groups, which use the Fmoc strategy to protect a -ammonia and in the form of their tertbutyl(tBu) esters to protect the side chain groups. And the L-Lys containsside chain ammonia, the protected product is Fmoc-L-Lys (Boc) .All the synthesis conditions were selected, and the purity of products are all higher than 97%.(1) The synthetic conditions of Fmoc-L-Lys (Boc) are:The protect reaction of side chain ammonia is stirring for 30h at 27 ℃,yield is 96.8%,the protect of a -ammonia is continue for stirring 2h at 30℃, yield is 91%.The total productivity is 88%.(2) The superior reaction conditions of all protected L-Ser, L-Thr are:The side chain hydroxyl group protect reaction of L-Ser is absorbing isobutylene in ice bath for 48h,the -ammonia protected reaction is in pH which is above 10,at -5℃ stirring for 36h.The total productivity is 89.2%.The same as L-Ser, protected L-Thr is also absorbing isobutylene in ice bath for 48h, the a -ammonia protected reaction is in pH which is above 10,at 0℃ stirring for 36h.The total productivity is 73%.(3) The reaction condition of Fmoc-L-Tyr (tBu) are:. The a -ammonia protected reaction is in pH which is above 10,at 0℃ stirring for 12h,the highest yield is 96%.The side chain protect reaction is absorbing isobutylene in ice bath for 6h, the highest yield is 83%. The total productivity is 79.6%. III Doing raw material costs estimation on the synthesized protect amino acidsThrough the control of reaction conditions, we can amplify the synthesis scale of protect amino acids and can decline the costs of them on a certain degree. The costs of all products are far below the merchandise, only the one tenth of merchandise, but the purity of each product is as high as the merchandise .