Synthesis method of Bremelanotide

Abstract

The invention discloses a preparation method of polypeptide, particularly relates to a synthesis method of Bremelanotide and belongs to the field of drug synthesis. The synthesis method comprises the following steps: two fragments of Bremelanotide are synthesized firstly and comprise a fragment with two amino acids and a fragment with five amino acids, p-hydroxymethylbenzoic acid is used for protecting the right side of a Bremelanotide sequence, namely, a carboxyl functional group of lysine, and the final product Bremelanotide is obtained with a counter-clockwise ring-forming synthetic method. The synthesis method has the advantages of being short in synthesis route, high in yield and low in synthesis difficulty and cost, and adopting cheap and available raw materials, and is suitable for industrial production.

Description

technical field

[0001] The invention relates to a preparation method of a polypeptide, in particular to a synthesis method of bremelanotide, which belongs to the field of drug synthesis. Background technique

[0002] Bremelanotide, also known as pomeratide and PT141, is an α-melanocyte stimulating hormone (α-melanocyte stimulating hormone, αMSH) polypeptide α analog with a cyclic heptapeptide structure. A large number of studies have confirmed that their receptor molecules play an important role in sexual arousal, appetite reduction, and catalyzing the synthesis of melanin, which can treat sexual dysfunction, obesity, and stimulate the skin to produce melanocortin to resist ultraviolet burns and other diseases. PT-141 is a drug for the treatment of sexual dysfunction developed by Palatin Corporation of the United States. It has completed phase III clinical trials and is effective for both male and female patients, especially the only effective drug candidate for female patie...

Examples

Embodiment 1

[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, ...

technical field

[0001] The invention relates to a preparation method of a polypeptide, in particular to a synthesis method of bremelanotide, which belongs to the field of drug synthesis. Background technique

[0002] Bremelanotide, also known as pomeratide and PT141, is an α-melanocyte stimulating hormone (α-melanocyte stimulating hormone, αMSH) polypeptide α analog with a cyclic heptapeptide structure. A large number of studies have confirmed that their receptor molecules play an important role in sexual arousal, appetite reduction, and catalyzing the synthesis of melanin, which can treat sexual dysfunction, obesity, and stimulate the skin to produce melanocortin to resist ultraviolet burns and other diseases. PT-141 is a drug for the treatment of sexual dysfunction developed by Palatin Corporation of the United States. It has completed phase III clinical trials and is effective for both male and female patients, especially the only effective drug candidate for female patie...

Examples

Embodiment 1

[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, ...