Study On Preparation Of Fmoc Series Protected Amino Acids

The use of peptide in the field of biology and medicine becomes more and more important along the development of biological technology. Protected amino acids are the significant raw materials of the solid phase peptide synthesis. All the amino acids have α-amido and carboxyl, some of the amino acids have lively side chain groups, such as hydroxyl, amido, guanidine and heterocyclic groups et al. In solid phase peptide synthesis, α-amido and lively side chain group are all protected before peptide synthesis, then removed by the chemical reagents after peptide synthesis, because unprotected amino acids will connect inaccurately or bring some side reactions.Protected amino acids can be separated as single protected amino acids and double protected amino acids, Single protected amino acids only have α-amido and double protected amino acids have α-amido and lively side chain group. In this dissertation, two kinds of protected amino acids including L and D type amino acids were discussed and the synthesis art and cost were investigated. Protected amino acids have been used in the lab of peptide synthesis.Single protected amino acids used base-labile Fmoc to protect amido, such as Fmoc-Gly-OH, Fmoc-L-Leu-OH, Fmoc-L-Ile-OH and Fmoc-D-Val-OH. Using single factor analysis, reaction time and temperature of Fmoc-Gly-OH and Fmoc-D-Val-OH were optimized. Optimum condition combination of Fmoc-L-Leu-OH and Fmoc-L-Ile-OH were got by L9(33)orthogonal experiment design. Double protected amino acids include D-Lys-OH with side amido and L-Arg-OH with side guanidine group. Fmoc, Boc and Pbf were used respectively to protect α-amido, side amido and side guanidine group. Main reaction conditions were optimized by using single factor analysis because of so many steps, including time and temperature of preparating Cu complexe and time of removing Cu ion. The reaction time of Z-Arg-OH, temperature of Z-L-Arg(Pbf)-OH·CHA,weight of catalyst, reaction pressure ,temperature and time of removing Z were investigated. The yields were higher. Reaction processes were inspected by T.L.C and the optimum crystal conditions were got. The purities determined by HPLC are all over 95.0% and physical constants including IR,MS and HNMR were measured.At last, the cost of each protected amino acids was calculated from amino acids raw materials, protecting reagents and accessorial materials ,which were contrasted with market price.