A kind of preparation method of unsaturated carbonyl-containing pharmaceutical small molecule
A small-molecule, unsaturated technology, applied in peptide preparation methods, chemical instruments and methods, drug combinations, etc., can solve the problems of changing drug functions, slow sulfhydryl exchange process, etc., and achieve the effect of high yield
Inactive Publication Date: 2016-08-24
CHANGZHOU UNIV +1
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Problems solved by technology
Although this sulfhydryl exchange reaction is widely used in intracellular drug release, the thiol exchange process is also slow (the half-life of the reaction is usually as long as more than ten hours), and the introduction of sulfhydryl groups on small molecule drugs often changes the drug properties. Function
Method used
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Embodiment 1
[0029] Such as figure 1 As shown, the drug small molecule Preparation: (1) D-ribose (80g, 532.9mmol) was dissolved in acetone 1000ml, and H was added dropwise at room temperature 2 SO 4 (2.4ml) and stirred at room temperature for 2.5 hours, the mixture was washed with solid NaHCO 3 Neutralized, filtered and concentrated by evaporation under reduced pressure to give a colorless syrup (1a), yield 74%.
[0030] (2) Compound 1a (20.36g, 107.1mmol) was dissolved in anhydrous THF (800ml), and vinylmagnesium bromide (480.0ml, 480.0mmol, 1.0M THF solution) was added dropwise at -78°C, and the reaction mixture was Stirring at 0°C for 3 hours afforded the compound (2a), the content of compound 2a (main product) in the product (2a+2b) is 74%.
[0031] (3) Compound 2a (19.25g, 88.2mmol) was used in CH 2 Cl 2 (330ml) solution, sodium periodate (204.0ml, 132.4mmol, 0.65M aqueous solution) solution was added dropwise at 0°C, and the reaction mixture was stirred at room temperature...
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Abstract
The invention provides a preparation method of medicine micro-molecules containing unsaturated carbonyl. The preparation method of medicine micro-molecules containing unsaturated carbonyl comprises the following steps: (1) dissolving D-ribose in acetone, stirring and dropwise adding concentrated sulfuric acid, neutralizing and purifying to obtain a compound 1a, wherein the chemical formula of the compound 1a is as shown in the specification; (2) dissolving 1a in a THF solution, dropwise adding vinylmagnesium bromide, reacting to obtain a compound 2a, wherein the chemical formula of the compound 2a is as shown in the description; (3) dropwise adding sodium periodate into a CH2Cl2 solution of 2a, and reacting to obtain a compound 3a, wherein the chemical formula of the compound 3a is as shown in the specification; (4) adding hydroxylamine hydrochloride and sodium bicarbonate into a methanol solution of 3a, and reacting to obtain a compound 3b, wherein the chemical formula of the compound 3b is as shown in the description; (5) dropwise adding a chloramines trihydrate into a suspension containing 3b and silica gel methanol, and reacting to obtain a compound 3c, wherein the chemical formula of the compound 3c is as shown in the description; (6) dissolving the compound 3c in dichloromethane, adding pyridine and dropwise adding TfO2, and reacting to obtain a compound 4a, wherein the chemical formula of the compound 4a is as shown in the description; (7) dissolving the compound 4a into anhydrous methylene chloride, refluxing, adding Et3N, and reacting to obtain a compound 4b, wherein the chemical formula of the compound 4b is as shown in the specification; and (8) dissolving the compound 4b into THF, adding Sml2 and reacting to obtain a compound 4c, wherein the chemical formula of the compound 4c is as shown in the description.
Description
technical field [0001] The invention belongs to the field of drug preparation, and relates to a method for preparing small drug molecules containing unsaturated carbonyl groups. Background technique [0002] With the improvement of people's living standards, the acceleration of the pace of life in modern society, the change of lifestyle, environmental pollution and many other factors, cancer has become the main killer of human health. In recent years, although great progress has been made in the diagnosis and treatment of tumors, the morbidity and mortality of common malignant tumors are still high. The targeted diagnosis and treatment of tumors has become one of the most important research directions in the field of tumor diagnosis and treatment. At present, the commonly used targeting molecules mainly use the ligands or antibodies of specific molecules on the surface of tumor cells as tumor targeting molecules. Engineering or chemical modification methods couple ligands o...
Claims
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IPC IPC(8): C07D317/48A61K47/48A61K31/36A61P35/00C07K7/06C07K1/107
Inventor 王建浩李静燕蒋鹏举邱琳李进晨王车礼秦玉琴滕一万柳丽周翔
Owner CHANGZHOU UNIV