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Application of New Reagent Tbfmoc-Met-OH for the Solid Phase Synthesis and Purification of Ubiquitin and Chemical Synthesis of Azabicyclo Drug Intermediates

Author: HuNaiFeng
Tutor: WangPu
School: Shandong University
Course: Medicinal Chemistry
Keywords: Tbfmoc-methioine ubiquitin solid phase peptide synthesis protein separation and purification azabicyclo conpounds drug intermediates
CLC: R914
Type: Master's thesis
Year: 2011
Downloads: 21
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Abstract


This thesis consists of two projects:one is chemical synthesis of new reagent Tbfinoc-Met-OH and using it as building block of ubiquitin in solid phase synthesis as well as the product purification helper; another is chemical synthesis of azabicyclo drug intermediates.In the first project, the new reagent Tbfmoc-Met-OH is synthesized in five steps, and then it is used as building block for the solid phase peptide synthesis (SPPS) of ubiquitin (Ub), a protein containing 76 amino acids and the N-terminal is methioine (Met), to introduce the Tbfmoc group into the N-terminal of ubiquitin. The synthetic Tbfinoc-Ub can show strong absorbance at 365 nm, be separated from the impurities efficiently due to its short retention time in gel filtration chromatography. The Tbfinoc group in the separated Tbfmoc-Ub can be removed under pH 8.5 condition, and the synthetic ubiquitin can be obtained with high efficiency and purity. The established purification strategy and the synthetic Tbfmoc-Met-OH will have important application value for other synthetic peptides and proteins.The second project concentrates on the chemical synthesis of azabicyclo conpounds including 6,7-dihydro-5H-pyrrolo (3,4-b) pyridine and 2,8-diazabicyclo (4,3,0) nonane, which are important structural units in various drugs and bioactive compounds, and play significant roles in the research fields of structure activity relationship and new drug discovery. By exploring, comparing and optimizing different methods and reaction conditions, the synthetic routes with mild reaction conditions and easy operation are established to synthesize the azabicyclo conpounds as well as their derivatives efficiently. The established routes in this project can overcome the weak points such as harsh reaction conditions, low yields and long reaction time in the present methods, and will become important basis for future research in this direction.

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CLC: > Medicine, health > Pharmacy > Drug basic science > Medicinal Chemistry
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