Liquid phase synthesizing method for bivalirudin
A bivalirudin, liquid-phase synthesis technology, which is applied to the preparation methods of peptides, chemical instruments and methods, blood diseases, etc., can solve the problems of difficulty in realizing large-scale synthesis, high production cost, and difficulty in large-scale production, etc. To achieve the effect of easy and safe production, simple equipment and safe production
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[0018] The present invention aims at synthesizing bivalirudin in liquid phase, and integrates the advanced method and technology of polypeptide synthesis by solid phase method and liquid phase method, through the orthogonal protection strategy of amino acids contained in bivalirudin, the selection of The optimization of reaction conditions, the purification of crude products and other factors were comprehensively analyzed, and a novel liquid-phase synthesis route of bivalirudin was designed, which can minimize the production of bivalirudin while ensuring product quality. synthetic cost.
[0019] Main technical route of the present invention is——
[0020] First synthesize three larger fully protected fragments: "Fragment A" N-terminal fully protected hexapeptide, R 1 -D-Phe-Pro-Arg(R 2 )-Pro-Gly-Gly-OR 3 ; The fully protected 6-peptide in the middle of "fragment B", R 1 -Gly-Gly-Asn-Gly-Asp(R 4 )-Phe-OR 3 ; "Fragment C" C-terminal fully protected 8-peptide, R 1 -Glu(R 4...
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