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A kind of preparation method and application of pentapeptide
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A technology of reaction and reaction flask, applied in the field of preparation of pentapeptides
Active Publication Date: 2019-01-25
安婕妤化妆品科技股份有限公司
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Some biotechnology companies in Shanghai and Shenzhen also sell such products, but there are few reports on the specific synthesis methods at home and abroad, and the domestic products are basically obtained through imports.
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Embodiment 1
[0093] 1) Synthesis of KTTKS-3 - CbzLys:
[0094] Add 10g of lysinehydrochloride, 75mL of water, and 12.7g of basic copper carbonate to the reaction flask in sequence, stir and reflux for 4 hours, then add 50mL of hot water at 60°C to 70°C, filter, cool the filtrate to 0°C, and use solid Na 2 CO 3 Adjust the pH value to 9, then add dropwise 10mL benzyl chloroformate (use solid Na 2 CO 3 Control the pH ≈ 9), after the dropwise addition, react at room temperature for 12 hours, and filter to obtain a blue solid; add 200 mL of water to the blue solid, add 8.42 g of hydrogensulfide while stirring, react at 50 ° C for 3 hours, and use 2mol / L Adjust the pH value to 2 with hydrochloric acid, boil for 5 minutes, filter, concentrate the filtrate to 60 mL, put it in the refrigerator at 0-4°C overnight to crystallize, filter, and dry in vacuo to obtain 3.8 g of CbzLys (white solid, yield 20.1%).
[0095] The reaction equation involved in this step is as follows:
[0096]
[0097]...
Embodiment 2
[0150] 1) Synthesis of PalKTTKS-1——palmitoyl chloride (PalCl):
[0151] 100mL SOCl 2 Add to the reaction kettle, keep the temperature at 0°C, add 10g of palmitic acid in batches, stir for 30min, then slowly raise the temperature to 60°C, reflux for 2h, and recover the solvent SOCl 2 , add acetone and evaporate to dryness to obtain 10.2g palmitoyl chloride (colorless transparent oily liquid, yield 99%).
[0152] 2) Synthesis of PalKTTKS-2——PalLysCbz:
[0153] Dissolve 2.8g of CbzLys in 15mL of 1mol / L NaOH solution, keep the temperature at 0°C, add 2.8g of palmitoyl chloride dropwise, react at room temperature for 4h after the dropwise addition, follow the TLC plate until the raw material disappears, filter to remove the solid to obtain the filtrate, and use dilute H 3 PO 4 Adjust the pH value to 2-4, precipitate a white solid, filter, and use H 3 PO 4 dilute solution, dried, and then CH 2 Cl 2 Recrystallization gave 4.45 g of PalLysCbz (white powder, yield 86.5%).
[01...
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Abstract
The invention discloses a preparation method and application of a pentapeptide. The preparation method of the pentapeptide comprises the following steps of (1) preparing CbzLys; (2) preparing CbzLysBoc; (3) preparing CbzLysBoc-SerO Me; (4) preparing CbzLys-SerOMe; (5) preparing R1LysR2; (6) preparing R1LysR2-ThrOMe; (7) preparing R1LysR2-Thr; (8) preparing R1LysR2-Thr-ThrOMe; (9) preparing R1LysR2-Thr-Thr; (10) preparing R1LysR2-Thr-Thr-CbzLys-SerOMe; (11) preparing R3Lys-Thr-Thr-CbzLys-SerOMe; (12) preparing R3Lys-Thr-Thr-CbzLys-Ser; (13) preparing a final product pentapeptide R3Lys-Thr-Thr-Lys-Ser. According to the preparation method of the pentapeptide, liquid-phase synthesis is adopted, a process is simple, the overall yield is 30 percent, and the method is low in side reaction rate and cost, short in reaction time and convenient for large-scale production, and has remarkable economic effects.
Description
technical field [0001] The invention relates to a preparation method and application of a pentapeptide. The pentapeptide has an amino acid sequence of Lys-Thr-Thr-Lys-Ser. Background technique [0002] Short peptides are simple peptide compounds with a molecular weight between 150 and 2000 Da and composed of less than 10 amino acids. They are also called oligopeptides, small molecule peptides or oligopeptides. Their structure is between amino acids and proteins. Short peptides are precise protein fragments. Their chemical stability and thermal stability are superior to those of proteins. They widely exist in living organisms and are easily absorbed by the body. They can fundamentally solve or alleviate various problems in the body. [0003] Short peptides have a variety of biological activities, are safe and efficient, and have incomparable advantages in various nutritional and health products, but they have not been widely used. The main reason is that there are many proble...
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