Synthesis Of Novel Amoni Acids And Their Derivates For Peptide Preparation

As the basic building block, amoni acid has received the wide attention of chemists. Just take the amoni acids and peptides used nowadays for the drug researching and syntheses of chiral drugs. The related study and production is on fast rise. New amoni acids and their derivates have always been the key point of chemists′research. This dissertation deals with the synthesis of some novel amoni acids derivates based on cheap and easy making materials.Using Ivdde as the terminal amino group protector for four amoni acids with different carbon chain length, which are Fmoc-Dap-OH, Fmoc-Dab-OH, Fmoc-Orn-O and Fmoc-Lys-OH, four derivates were obtained named as Fmoc-Dap(Ivdde)-OH, Fmoc-Dab(Ivdde)-OH, Fmoc-Orn(Ivdde)-OH and Fmoc-Lys(Ivdde)-OH respectively. The synthetic procedure of the four amoni acids in our work has been proved to be of feasible value and can be applied into large scale production.Our second part of work based on the fact that enantiopure non-proteinogenic amino acids play a major role in the synthesis of peptidomimetics like HIV protease inhibitors, thrombin inhibitors and inducers for the for-mation ofβ-turns to influuence protein folding. Especially 3,(4)-substituted prolines1 and (pyro)glutamates as building blocks in bioactive peptides can give additional information about receptor recognition1fand affinity. (S)-Pyroglutamic acid was transformed into the Cbz-protected 4-methyl-2,6,7-trioxabicyclo[2.2.2] octane (OBO) ester. This ortho ester functionality was employed as a bulky steering group for stereoselective introduction of alkyl and aryl groups via 1,4-cuprate addition to 3,4-unsaturated pyroglutamates. After deprotection and ring-opening, (2s,3s)-3-methyl-glutamic acid was obtained successfully in the current work.