Cyclodextrin-camptothecin type supermolecules chemotherapeutic drugs, and preparation and applications thereof
A technology of cyclodextrin and camptothecin, applied in the field of biomedical technology, supramolecular chemistry and drug controlled release, and nanomedicine, can solve the problem of drug efficacy decline
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Embodiment 1
[0083] Embodiment 1: the preparation of CPT-S-S-OH (1)
[0084] With stirring at room temperature, 4-dimethylaminopyridine (2.10 g, 17.2 mmol) was added to a solution of camptothecin (2.00 g, 5.74 mmol) in dichloromethane. After continuing to stir for 30 minutes, triphosgene (0.633 g, 2.12 mmol) was added slowly. After stirring for 1 hour, 2,2'-dithiodiethanol (17.2 g, 117 mmol) was added dropwise, and the reaction solution was stirred overnight at room temperature. The mixture was washed three times with saturated brine (100 mL), and the dichloromethane organic phase obtained by separation was dried over anhydrous sodium sulfate. The product was purified by flash chromatography using a prepacked silica column. Yield: 2.12 g (70% yield). 1 H NMR (300MHz, CDCl 3 ): 8.46 (s, 1H), 8.22 (d, J=8.3Hz, 1H), 7.99 (dd, J=8.2, 1.1Hz, 1H), 7.86 (ddd, J=6.9, 6.5Hz, 1H), 7.70 (ddd, J=8.1, 6.9, 1.2Hz, 1H), 7.42(s, 1H), 5.64(d, J=18Hz, 1H), 5.36(m, 1H)4.37(t, J=6.0Hz, 2H) , 3.93-3.81 (...
Embodiment 2
[0085] Embodiment 2: the preparation of CPT-S-S-COOH (2)
[0086] Dissolve the CPT-S-S-OH (300mg, 0.552mmol) prepared by Example Method 1 in anhydrous dichloromethane under stirring, add succinic anhydride (1.00g, 10.0mmol) and a small amount of 4-dimethylaminopyridine respectively (21.0mg, 0.172mmol), the reaction solution was stirred overnight at room temperature. After the solution was dried, the solid was washed with water (100 mL) three times, and dried in vacuo to obtain the product CPT-S-S-COOH (yield 88%). 1 H NMR (300MHz, CDCl 3 ): 8.44 (s, 1H), 8.32 (d, J = 8.4Hz, 1H), 7.95 (d, J = 8.2Hz, 1H), 7.84 (ddd, J = 8.5, 6.9, 1.4Hz, 1H), 7.69 (ddd, J=8.1, 7.0, 1.1Hz, 1H), 7.43(s, 1H), 5.71(d, J=17.3Hz, 1H), 5.39(d, J=17.3Hz, 1H), 5.32(s, 2H), 4.46-4.25 (m, 4H), 3.00-2.86 (m, 4H), 2.79-2.61 m, 2H), 1.01 (t, J=7.5, 3H). ESI-MS m / z: calculated value 628.12, found value 629.10 (M+H) + . figure 2 for CPT-S-S-COOH 1 The H NMR spectrum proves that the compound was successfu...
Embodiment 3
[0087] Embodiment 3: the preparation of CD-S-S-CPT
[0088] The CPT-S-S-COOH (628 mg, 1.00 mmol) prepared by the method in Example 2 was dissolved in 100 ml of anhydrous dichloromethane. Add N-hydroxysuccinimide (0.575g, 5.00mmol), 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl, 1.91g, 10.0mmol ), stirred at room temperature for 1 day. The organic solvent was removed using a rotary evaporator, and the mixture was washed 3 times with chilled methanol (100 mL). The obtained white solid (363mg, 0.500mmol) was dissolved in DMF (20ml), 6-ethylamino-β-cyclodextrin (1.18g, 1.00mmol) and three drops of triethylamine were added respectively, and stirred overnight at room temperature. The solution was poured into 100 ml of acetone, suction filtered to obtain a light yellow solid, washed three times with dichloromethane (100 ml), washed three times with water (50 ml), and the solid was drained to obtain the product CD-S-S-CPT (yield 74%). 1 H NMR (300MHz, CDCl 3 ...
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