Studies On The Synthesis And Biological Activity Of The Derivative Of Peptide Drug Oxytocin

Oxytocin is the first hormone that has biological activity by synthesis which can provoke uterus to contract and uterus neck to mature. It was not only used extensively as oxytocic but also used to prevent hemorrhage after delivery. The studies of conformation-activity of oxytocin indicated that it is feasible to modificate oxytocin in structure to some extent. There are many analogues of oxytocin have been obtained in this process and some useful are selected as new peptide drugs clinically.Althrough a half century almost past from the beginning of the research of oxytocin, there is few about acyclic oxytocin. On the basis of isoteric principle, this thesis is concentrates on the synthesis and biology activities of an analogue of oxytocin in which the cysteine group in 1- and 6- of oxytocin are replaced by its isoteric group L- α ,β -diaminopropionc acid.The aim compound, the novel derivative of oxytocin containing nonprotein amino acid L-a,p-diamiopropionic acid (L-Dap) was synthesized by 7+2 fragment combination in solution. N° of all the amino acid necessary was protected by carbobenzoxy (Z) and N^β of L-Dap was protected by tert.-butoxycarbonyl (Boc). The important intermediate, heptapeptide, was synthesized by the stepwise elongation method using carbobenzoxy amino acid p-nitrophenyl esters by solution technique. Azide synthesis was used to get the nonapeptide. Z group was removed by treatment with 5% Pd/C and Boc with CF₃COOH. Recrystallization and solvent refluxing are used for the refine of the intermediate. For the aim compound, gel and HPLC are tried. 96.4% purity is obtained by HPLC and freeing dryness. Thirty compounds were synthesized and eight new compounds...