Synthesis method of Bremelanotide
A synthesis method and carboxyl technology, applied in the field of pharmaceutical synthesis, can solve the problems of long synthesis route, many steps, low yield and the like, and achieve the effect of improving yield
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[0026] 1. Preparation of HMBA-Rink-Amide-AM-resin resin
[0027] Take out the Rink-Amide-AM-resin resin, put it into the glass polypeptide reaction column, wash it once with DMF, then swell it with DCM for about 20 minutes, and remove the DCM; add 4 times the amount of HMBA linker, HOBt, DIC, coupling reaction for 2 hours, Kaiser reagent detection, if there is no color, it means that the reaction is complete, if there is color, it means that the reaction is not complete, repeat the coupling process until the reaction is complete. It was then washed four times with DMF.
[0028] 2. Preparation of Fmoc-Lys(IVDde)-HMBA-Rink-Amide-AM-resin resin
[0029] Add Fmoc-Lys(IVDde)-OH, HOBt, DMAP, and DIC mixed with DMF into the glass polypeptide reaction column in step 1. The molar ratio between them and the resin is (3 / 3 / 0.3 / 3.6): 1. For more than 5 hours, then wash four times with DMF, add 20-30 times the amount of acetic anhydride and pyridine mixture (ratio: 2:1), block overnight, ...
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