7-Ethylcamptothecin

7-Ethylcamptothecin is one of camptothecin analogues. camptothecin (CPT), a cytotoxic alkaloid isolated from Camptotheca acuminate, is shown to have strong antitumor activity against L1210 leukemia and Walker 256 carcinosarcoma models[1].

Adding 80 g of camptothecin, 840 g of glacial acetic acid and 368 g of concentrated sulfuric acid to a 5 L reactor, and then mechanically stirring, after total dissolution80 g of propionaldehyde was added, and 102 g of hydrogen peroxide was further added thereto, and the reaction was carried out at a temperature of -5 to 5 ° C for 10 minutes. Add 10 kg of purified water to the system and mix itCrystal 2h, suction filtration to obtain 72.5 g of 7-ethylcamptothecin, the yield was 95.4percent.Under an argon atmosphere, In an ice bath, 6 (14 mg, 0.037 mmol, 1 eq) was dissolved in dry THF (20 mL), then pyridine (6 mg, 0.074 mmol, 2 eq) was stirred for 5 min.Diphosgene (8 mg, 0.04 mmol, 1.1 eq) was quickly added to the above solution with vigorous stirring and stirred for 1 hour.Unreacted phosgene was then removed by bubbling with argon.4-dimethylaminopyridine (0.5 mg, 0.005 mmol, 0.14 eq), triethylamine (33 muL, 0.24 mmol, 6.5 eq), compound 1 (18 mg, 0.04 mmol, 1.1 eq) and To a solution of General procedure: To a mixture of Biotin or 6-biotinylaminocaproic acid (0.3 mmol), General procedure: To a mixture of Biotin or 6-biotinylaminocaproic acid (0.3 mmol), General procedure: To a mixture of Biotin or 6-biotinylaminocaproic acid (0.3 mmol), The co-drug R-0-CO(CH2)2-CO-0-CH2-CO-OR1 in which R is an a-tocopherol moiety and OR1 is an SN-22 residue can be prepared by the following method. First, 3- (D-a-Tocopheryloxycarbonyl)propionyloxyacetic acid is prepared from the commercially available D-a-tocopheryl hemisuccinic acid. Briefly, tetrabutylammonium D- - tocopheryl hemisuccinate is reacted with tert-butyl bromoacetate in l-methyl-2- pyrrolidone (1-MP), with subsequent removal of the tert-butyl group with trifluoroacetic acid/triethylsilane in dichloromethane to yield the acid. SN-22 is then conjugated to this acid according to a standard procedure using l-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride (EDC) as a promoter and 4-N, N- dimethylamino-pyridine tosylate (DPTS) as a catalyst in dichloromethane as a solvent.General procedure: 7-Et-CPT (0.75'g, 2'mmol), EDCI (1.53g, 8'mmol) and DMAP (1.47'g, 12'mmol) were added to a solution of m-nitrobenzoic acid (1.00'g, 6'mmol) in 100'mL of CH2Cl2 with stirring at 2?°C for 15'min. The mixture was stirred at room temperature for 2'h and was poured onto 100'ml ice water. The obtained organic layer was washed with dilute hydrochloric acid and saturated salt water in turn, and concentrated. The crude product was chromatographically separated with CH2Cl2-THF as eluent. The pure product 3g (0.81'g) was obtained as almost white powder, yield 77.1percent, purity 98.97percent (HPLC), mp 272-274?°C. 1H NMR (CDCl3, 500'MHz) delta: 1.11 (t, J?=?7.5'Hz, 3H, 19-H), 1.40 (t, J?=?7.8'Hz, 3H, 30-H), 2.37-2.49 (m, 2H, 18-H), 3.20 (q, 2H, 29-H), 5.25 (d, J?=?18.5'Hz, 1H, 5-H), 5.29 (d, J?=?19.0'Hz, 1H, 5-H), 5.49 (d, J?=?17.0'Hz, 1H, 17-H), 5.79 (d, J?=?17.0'Hz, 1H, 17-H), 7.25 (s, 1H, 14-H), 7.68 (m, 2H, 10, 27-H), 7.77 (t, J?=?7.5'Hz, 1H, 11-H), 8.13 (t, J?=?9.8'Hz, 2H, 9, 12-H), 8.40 (d, J?=?7.5'Hz, 1H, 24-H), 8.46 (m, 1H, 26-H), 8.93 (s, 1H, 28-H). ESI-MS m/z: 526.2 (M?+?1)+.

An anticancer drug, showed strong activity against various murine tumors.A Camptothecin (CPT) derivative as antineoplastic agent against drug-resistant tumors.

Molecular Weight:376.4
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:376.14230712
Monoisotopic Mass:376.14230712
Topological Polar Surface Area:79.7
Heavy Atom Count:28
Complexity:787
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes