Compound, and separation method, synthesis method and use thereof
AssigneeBeijing Peking University WBL Biotech Co., Ltd.
InventorsZhenwen Duan, Shuren Guo, Xuemei Li
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Abstract
The invention relates to new compounds as well as a separation method, a synthetic method and use thereof. It is demonstrated by an assay on activity that the compound has an activity of inhibiting an HMG-CoA reductase. In addition, the invention also relates to a derivative of the compound.
Claims34
A compound of Formula (I), or a stereoisomer, tautomer, racemate, or pharmaceutically acceptable salt thereof:
- R1 is selected from H, C1-C6 alkyl, halo C1-C6 alkyl, (CH2)1-6OH, C3-C7 cycloalkyl, halo C3-C7 cycloalkyl, C1-C6 alkoxy, halo C1-C6 alkoxy, C1-C6 alkylthio, halo C1-C6 alkylthio, halogen, nitro, amino and cyano;
- R2 is selected from H, C1-C6 alkyl, halo C1-C6 alkyl, (CH2)1-6OR6, C3-C7cycloalkyl, halo C3-C7 cycloalkyl, C1-C6 alkoxy, halo C1-C6 alkoxy, C1-C6 alkylthio, halo C1-C6 alkylthio, halogen, nitro, amino and cyano;
- R3 is selected from H, C1-C6 alkyl;
- R4 and R5 each are independently selected from:
- H, —COR7, —SO2R8, and —SiR9R10R11;
- wherein, R7 is selected from C1-C6 alkyl and halo C1-C6 alkyl;
- R8 is selected from C1-C6 alkyl, optionally substituted C1-C6 alkyl, C6-C10 aryl, and optionally substituted C6-C10 aryl;
- R9, R10 and R11 are independently selected from C1-C6 alkyl;
- wherein, R6 has the same definition as R4 and R5;
- wherein, the following compounds are excluded;
- the compound of Formula (I) wherein R1 is (CH2)OH, R2 is methyl, and R3, R4 and R5 are H, and
- the compound of Formula (I) wherein R1, R3, R4 and R5 are H and R2 is methyl.
The following compound, selected from:
- and diacetate, bis(4-methylbenzenesulfonate), bis(trifluoromethanesulfonate), and bis(tert-butyldimethylsilyl ether) of Compound 5;
- and triacetate, tri(4-methylbenzenesulfonate), tri(trifluoromethanesulfonate), and tri(tert-butyldimethylsilyl ether) of Compound 5a.
A method for extracting Compound 5 from Monascus-fermented rice or extract thereof, comprising the following steps of:
- 1) extracting Monascus-fermented rice or extract thereof with ethyl acetate (or dichloromethane or methanol or ethanol, or methanol/ethanol aqueous solution) as a solvent;
- 2) separating the ethyl acetate (or dichloromethane or methanol or ethanol, or methanol/ethanol aqueous solution) extract obtained in Step 1) by silica gel column chromatography, and carrying out gradient elution with petroleum ether, ethyl acetate and methanol, to obtain the ethyl acetate eluting fraction;
- 3) separating the ethyl acetate eluting fraction obtained in Step 2) by silica gel column chromatography, carrying out elution with dichloromethane-ethyl acetate-methanol, detecting and combining the fractions, to obtain the fractions in Step 3);
- 4) separating the second fraction obtained in Step 3) by C18 column chromatography, and carrying out gradient elution with acetonitrile-methanol-water, to obtain 82% (acetonitrile-methanol 1:1) aqueous solution eluting fraction;
- 5) further separating the 82% (acetonitrile-methanol 1:1) aqueous solution eluting fraction obtained in Step 4) by sephadex LH-20 column chromatography using dichloromethane-methanol as a mobile phase, analyzing and combining the fractions, to obtain the fractions in Step 5);
- and
- 6) purifying the third fraction obtained in Step 5) by chromatographic method, to obtain Compound 5.
A method for synthesizing compound 5:
A method for synthesizing Compound 5:
Dependencies are inferred from the claim text.