- Novel idarubicin hydrochloride compound
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Disclosed is a novel idarubicin hydrochloride omega-type compound. The novel idarubicin hydrochloride omega-type compound has low hygroscopicity and high storage stability, is beneficial to drug quality control and the like, and is applicable to preparation of drugs for treating or preventing acute leukemia, advanced breast cancer, diffuse large B cell lymphoma of central nervous systems, non-Hodgkin's lymphoma, myelodysplastic syndrome, lung cancer, melanoma, soft tissue sarcoma, multiple myeloma, liver cancer, colorectal cancer, kidney cancer, prostate cancer, endometrial cancer, testiculartumor, ovarian cancer, head and neck cancer, and the like.
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Paragraph 0128-0129
(2020/03/12)
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- Preparation method for idarubicin hydrochloride
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The invention belongs to the field of drug synthesis, and discloses a preparation method for idarubicin hydrochloride. The idarubicin hydrochloride is prepared by adopting a metal nickel catalyst / anorganic phosphine ligand / a silane reducing agent to remove a methoxy group located at a 4-position of an anthracycline compound in one step. According to the invention, the method has the advantages that the steps are short and the synthesis costs are reduced, can reduce generation of an impurity A and an impurity B, and improves the quality of the final product idarubicin hydrochloride.
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- CRYSTALLIZATION OF IDARUBICIN HYDROCHLORIDE
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A method is provided for production of crystalline idarubicin hydrochloride, the method including the steps of: (i) producing a mixture containing (a) idarubicin hydrochloride, (b) at least one alcohol selected from 1-butanol, 2-butanol, and 1-pentanol, and (c) water; and (ii) crystallizing idarubicin hydrochloride from this mixture. A crystalline idarubicin hydrochloride is also provided characterized by a powder x-ray diffraction pattern in which at least reflexes at diffraction angles occur in the following ranges (in 2Θ): 7.2-7.7; 11.7-12.2; 16.2-16.7; 16.7-17.2; 19.6-20.1; 19.8-20.3; 22.2-22.7, and 22.9-23.4.
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Paragraph 0091
(2014/08/19)
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- METHOD OF PRODUCING 4-DEMETHOXYDAUNORUBICIN
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The present invention relates to a method for the synthesis of 4-demethoxydaunorubicin (idarubicin) having the chemical structure of formula (I), which involves the demethylation of 3′-Prot-daunorubicin in the presence of a soft Lewis acid. The method of the present invention does not comprise cleavage of the glycosidic linkage at carbon C7, thus resulting in a faster synthesis cycle and an improved yield of the final product.
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Page/Page column 8-9
(2012/11/08)
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- Method of preparing 4-R-substituted 4-demethoxydaunorubicin
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A method of synthesizing 4-R-substituted anthracyclines and their corresponding salts from 4-demethyldaunorubicin includes the steps of treating 4-demethyldaunorubicin with a sulfonylating agent to form 4-demethyl-4-sulfonyl-R3-daunorubicin. 4-Demethyl-4-R3-sulfonyl-daunorubicin is then subject to a reducing agent in the presence of a transition metal catalyst in a temperature range of about 30° C. to about 100° C. in a polar aprotic solvent in an inert atmosphere. Protected 4-demethoxy-4-R-daunomycin then undergoes hydrolysis in a basic solution to form the 4-R-substituted anthracyclines. The novel method lacks the step of forming a stereospecific glycoside bond between aglycone and aminoglycoside. The method also increases the yield of the final product up to 30 to 40%.
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- Process for an anthracycline derivative, and an anthracyclinone derivative useful for the process
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A process for producing an anthracycline derivative represented by the general formula: STR1 where R1 is an acyl group, each of X1 and X2 is a hydrogen atom, a methoxy group, a hydroxyl group, a halogen atom or a lower alkyl group, each of Y1 and Y2 is a hydrogen atom, an alkoxy group or a hydroxyl group, and Z is a hydrogen atom or a protected hydroxyl group, which comprises reacting an anthracyclinone derivative represented by the general formula: STR2 where R is a hydrogen atom or a trialkylsilyl group, and X1, X2, Y1, Y2 and Z are as defined above, with a 1-acyl-sugar derivative represented by the general formula: STR3 where R2 is an acyl group and R1 is as defined above, in the presence of a silyl sulfonic acid derivative represented by the general formula: where each of R3, R4 and R5 is an alkyl group and A is an alkyl group, an aryl group, a polyfluoroalkyl group or a hydrogen atom.
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- TRIMETHYLSILYL TRIFLUORMETHANESULFONATE (TRIMETHYLSILYL TRIFLATE) AS AN EXCELLENT GLYCOSIDATION REAGENT FOR ANTHRACYCLINE SYNTHESIS. SIMPLE AND EFFICIENT SYNTHESIS OF OPTICALLY PURE 4-DEMETHOXYDAUNORUBICIN
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The title reagent was found to effect the glycosidation of (+)-4-demethoxyanthracyclinones with N-trifluoracetyl-1,4-di-O-p-nitrobenzoyl-L-daunosamine, giving the α-glycosides in 99percent yields.Sequential deprotections of the glycoside readily afforded optically pure (+)-4-demethoxydaunorubicin.
- Kimura, Yoshikazu,Suzuki, Michiyo,Matsumoto, Teruyo,Abe, Rumiko,Terashima, Shiro
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p. 501 - 504
(2007/10/02)
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