Method For Synthesizing Degarelix

A method for synthesizing degarelix, comprising the following steps:

• step 1:
• condensing a protected D-alanine with an amino resin under the action of a condensation reagent and an activation reagent to obtain a peptide resin 1;
• step 2:
• sequentially extending and coupling a protected Pro, protected Lys(ipr), protected Leu and Boc-D-Aph(Fmoc) by starting from the peptide resin 1 according to the order from C-terminus to N-terminus of the amino acid sequence of degarelix under the action of the condensation reagent and the activation reagent, and then removing the side chain Fmoc protective group in Aph(Fmoc) to generate D-Aph(NH2), to obtain a peptide resin 2, wherein the protected Lys(ipr) is a protected Lys(ipr, Z);
• step 3:
• reacting the side chain amino group in D-Aph(NH2) in the peptide resin 2 with tert-butyl isocyanate under the catalysis of an organic base to generate D-Aph(tBu-Cbm), to obtain a peptide resin 3;
• step 4:
• sequentially extending and coupling a protected Aph(Boc), protected Ser(Bzl), protected D-Pal, protected D-Cpa, protected D-Nal and Ac2O by starting from the peptide resin 3 according to the order from C-terminus to N-terminus of the amino acid sequence of degarelix under the action of the condensation reagent and the activation reagent, to obtain a peptide resin 4;
• step 5:
• removing the side chain Boc protective group in the protected Aph(Boc) in the peptide resin 4, and incorporating L-4,5-dihydroorotic acid under the action of the condensation reagent and the activation reagent to obtain a degarelix resin;
• step 6:
• acidolysing the degarelix resin by an acidolysis agent to obtain a crude degarelix, wherein the acidolysis agent is a solution of hydrogen bromide in trifluoroacetic acid;
• and
• step 7:
• purifying the crude degarelix to obtain a pure degarelix.