反应详情

1.1 g (5 mmol) of Phe-Gly (manufactured and sold by PEPTIDE INSTITUTE INC., Japan) was dissolved in a mixture of 2 ml of water, 2 ml of 2-propanol and 1.5 ml of diethylamine to obtain a solution. To the obtained solution was gradually added 1.8 g (6.5 mmol) of trityl chloride, followed by stirring for one hour. To the resultant reaction mixture was added water, to thereby generate a precipitate. The generated precipitate was collected, washed with water and then dissolved in 5 ml of acetic acid, to thereby obtain an acidic solution. The solvents were distilled off from the obtained acidic solution under reduced pressure, to thereby obtain 1.5 g of Trt-Phe-Gly. 604 mg (1.3 mmol) of the obtained Trt-Phe-Gly, 158 mg (1.3 mmol) of DMAP and 853 mg (1.0 mmol) of paclitaxel were dissolved in 20 ml of methylene chloride to obtain a solution. To the obtained solution was added 164 mg (1.3 mmol) of DIPC and stirred overnight at room temperature to effect a reaction. After completion of the reaction, the solvents were distilled off from the resultant reaction mixture under reduced pressure. The resultant residue was purified by silica gel column chromatography (silica gel: Art No. 9385, Silica gel 60, 200-400 mesh, manufactured and sold by Merck KGaA, Germany; column: 4.0×30 cm; eluent: methylene chloride/acetonitrile ratio=80/20), to thereby obtain 980 mg of 2′-Trt-Phe-Gly-paclitaxel. 800 mg of the obtained 2′-Trt-Phe-Gly-paclitaxel was treated with 10 ml of 90% acetic acid to effect a reaction for removing an N-trityl group. The resultant product was purified by silica gel column chromatography (silica gel Art No. 9385, Silica gel 60, 200-400 mesh, manufactured and sold by Merck KGaA, Germany; column 4.0×30 cm; eluent: methylene chloride/methanol/acetonitrile ratio=95/5/5), and subsequently converted from an acetate to a corresponding hydrochloride with an ion exchange resin, to thereby obtain 450 mg of 2′-Phe-Gly-paclitaxel hydrochloride (186).

1. customto obtain a solution
2. customTo the resultant reaction mixture
3. customThe generated precipitate was collected
4. washwashed with water
5. dissolutiondissolved in 5 ml of acetic acid
6. customto thereby obtain an acidic solution
7. distillationThe solvents were distilled off from the obtained acidic solution under reduced pressure