Compound with antitumor activity and preparation method thereof
An anti-tumor drug and compound technology, applied in the field of compounds with anti-tumor activity and their preparation, can solve the problems of precipitation, inconvenience in use, high toxicity and the like of the preparation, and achieve enhanced immunomodulatory activity, improved pharmacodynamic index, good water soluble effect
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[0051] The preparation method of the compound of the present invention, it is by the compound shown in formula (II) and the Thymopentin C-terminal carboxyl group of protection in the presence of condensation reagent, the product that obtains after condensation reaction deprotects with deprotection reagent, purifies, freeze-dried,
[0052]
[0053] Further, paclitaxel pentapeptide and docetaxel pentapeptide are formed by reacting the 2'-hydroxyl group of paclitaxel or docetaxel and the protected thymopentin C-terminal carboxyl group in the presence of a condensation reagent to generate protected paclitaxel pentapeptide Or docetaxel pentapeptide, deprotected by deprotection reagent, purified by high performance liquid chromatography and freeze-dried.
[0054] The protected thymopentin used in the above preparation method is selected from the following protected thymopentin structures, and the preferred structure is protected thymopentin structure III.
[0055] Protect thymop...
Embodiment 1
[0062] Embodiment 1 prepares paclitaxel pentapeptide
[0063] Take protected thymopentin structure I [Fmoc-Arg(Pbf)-Lys(Boc)-Asp(OtBu)-Val-Tyr(tBu)-OH] 32.8g (24mmol), paclitaxel 10.2g (12mmol), 1-hydroxy -Benzo-triazole 3.3g (24mmol) and 4-dimethylaminopyridine 0.15g (1.2mmol), dissolved with 50ml N,N-dimethylformamide, stirred and added dropwise N,N-diisopropyl Carbodiimide 3.7ml, stirred at room temperature and reacted overnight, poured the reaction solution into 500ml of ice water, stirred well, collected the precipitate by filtration, and washed with water 3 times.
[0064] Add 50ml of 20% piperidine / N,N-dimethylformamide to the precipitate, stir and react at room temperature for 1 hour, pour the reaction solution into 500ml of ice water, stir well, collect the precipitate by filtration, and wash with water 3 times, 40 °C and dried under reduced pressure overnight.
[0065] Add 300ml of deprotecting agent (trifluoroacetic acid: triisopropylsilane: dimercaptoethylene gly...
Embodiment 2
[0066] Embodiment 2 prepares paclitaxel pentapeptide
[0067] Take protected thymopentin structure II [Fmoc-Arg-Lys(Boc)-Asp(OtBu)-Val-Tyr(tBu)-OH] 26.7g (24mmol), paclitaxel 10.2g (12mmol), 1-hydroxy-benzo - Triazole 3.3g (24mmol) and 4-dimethylaminopyridine 0.15g (1.2mmol), dissolved with 50ml N,N-dimethylformamide, stirred dropwise N,N-diisopropylcarbodiethylene Add 3.7ml of amine, stir at room temperature overnight, pour the reaction solution into 500ml of ice water, stir well, collect the precipitate by filtration, and wash with water 3 times.
[0068] Add 50ml of 20% piperidine / N,N-dimethylformamide to the precipitate, stir and react at room temperature for 1 hour, pour the reaction solution into 500ml of ice water, stir well, collect the precipitate by filtration, and wash with water 3 times, 40 °C and dried under reduced pressure overnight.
[0069] Add 300ml of deprotecting agent (trifluoroacetic acid: triisopropylsilane: dimercaptoethylene glycol: water = 94:2:2:2)...
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