Studies On Solution Phase Synthesis Of Octreotide And Protecting Group Of Amino Acids

Solution-phase synthesis is a classical method for peptide synthesis. Various coupling methods and strategies have been applied in formation of peptide. Intermediates of every step are separated and purified. Therefore it can be simply enlarged for commercial production.Octreotide, as somatostatin (SST) analogs, has been widely used in clinic therapy, because of its identified mechanism of action. In this dissertation, a process for commercial production using solution peptide chemistry and inexpensive amino acid derivatives was designed, in which fragment condensation were involved. Orthonal combined protecting systems, such as Boc-pMeOBzl and Boc-Z, as while as variousactive and coupling methods—azide method, carbodiimide method and active estermethod were adopted. The structures of the key intermediates and target molecule were confirmed by IR, MS and HPLC spectra data. Total yield was 28%.For supplement the above study, seven different Bzl type protecting groups were introduced into thiol of cysteine. T_1/2 of removal of the protecting groups in different concentration TFA was studied, in order to develop easily removal groups for solution peptide synthesis. It was found that increasing the number of electric donating group of aromatic would weaken the stability of the protecting group in acid condition, however, the introducing reaction of protecting group was difficult.In addition, the preparation of Orthonal protecting Lysine was improved by using 9-BBN as temporary protecting agents giving stable yield and less by-product.