CN110078774A - A kind of non-glucose carbon glycosides dihydrochalcone and preparation method thereof - Google Patents
A kind of non-glucose carbon glycosides dihydrochalcone and preparation method thereof Download PDFInfo
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Abstract
The present invention provides a kind of non-glucose carbon glycosides dihydrochalcones, it is characterized in that, the non-glucose carbon glycosides dihydrochalcone is compound with the following general formula I or the non-glucose carbon glycosides dihydrochalcone is the acceptable salt that compound with the general formula I and inorganic acid or organic acid are formed；Wherein, in the general formula I, A includes disaccharide base, any one in monosaccharide groups；The monosaccharide groups include the monosaccharide groups in addition to glucosyl group；R represent substituent group include 1-4 member alkyl, halogen replace 1-4 member alkyl, 3-4 member alkenyl, 3-4 member alkynyl, 3-6 member naphthenic base, halogen replace 3-6 member naphthenic base in any one.Non-glucose carbon glycosides dihydrochalcone provided in the embodiment of the present invention can accelerate hypoglycemic onset time under less toxic side effect, be effectively improved the sugar tolerance of diabetic.
Description
Technical field
The present invention relates to chemical synthesis and pharmaceutical field, more particularly to a kind of non-glucose carbon glycosides dihydrochalcone, with
And a kind of preparation method of non-glucose carbon glycosides dihydrochalcone.
Background technique
It is counted according to International Diabetes Federation, global diabetic's number is more than 400,000,000, and Chinese patients are more than 100,000,000, Huan Zheren
Number is gradually increasing, it is contemplated that the year two thousand forty, global patient estimated 6.42 hundred million.In recent years, rapid growth is presented in diabetes mellitus in China disease incidence
Situation occupies the 11.6% of adult population, increases 10 percentage points the year-on-year eighties in last century.National Wei Jianwei tables of data
Bright, China's diabetic population is up to 1.14 hundred million people, and wherein diabetes B accounts for nearly the 90% of diabetic population.Domestic public data
It has been shown that, domestic antidiabetic medicine point-of-sale terminal market is more than 50,000,000,000 yuan within 2017.
There are many deficiencies, such as hypoglycemic speed to lead to very much hypoglycemia, stomach fastly for various hypoglycemic drugs currently on the market
Adverse reaction is serious or administration mode is inconvenient etc..Domestic common oral hypoglycemic agents can be divided into five classes at present, i.e., biguanides,
Sulfonylurea, alpha-glucosidase restrainer, thiazolidinediones, meglitinide.Oral hypoglycemic agents hypoglycemic is rapid and effect is bright
It is aobvious, but have certain side effect, such as easily cause hypoglycemia, digestive tract reaction, lactic acidosis.It is existing currently on the market
The Chinese medicine majority for treating diabetes can alleviate the symptom of diabetes, and toxic side effect is small, but hypoglycemic is slow.Such as it is mentioned from Hainan blackberry lily
The active component (sea sugar is flat) taken is obvious for diabetic mice blood sugar decreasing effect, does not find apparent adverse reaction, safety
It is higher, wherein main effective component is known compound-swertisin and its derivative.
Therefore, the characteristics of carrying out structure of modification to the effective component of existing Chinese medicine, not only retained its safety is needed, but also is improved
Traditional Chinese medicine works slow deficiency.
Summary of the invention
While capable of guaranteeing safety technical problem to be solved by the invention is to provide one kind, improve existing hypoglycemic
The compound for the deficiencies of drug effect is slow, and while can guarantee safety, improve existing hypoglycemic drug work it is slow etc.
The preparation method of insufficient compound.
To solve the above-mentioned problems, the invention discloses a kind of non-glucose carbon glycosides dihydrochalcone, the non-glucose
Carbon glycosides dihydrochalcone is that the compound or the non-glucose carbon glycosides dihydrochalcone with the following general formula I are with described
The acceptable salt that the compound and inorganic acid or organic acid of general formula I are formed；
Wherein, in the general formula I, A includes disaccharide base, any one in monosaccharide groups；The monosaccharide groups include removing grape
Monosaccharide groups outside glycosyl.
The substituent group that R is represented includes 1-4 member alkyl, the 3-4 member alkenyl, 3-4 member alkynyl, 3- of 1-4 member alkyl, halogen substitution
6 yuan of naphthenic base, halogen replace 3-6 member naphthenic base in any one.
Optionally, the 1-4 member alkyl include methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl group, in tert-butyl
Any one.
Optionally, the 1-4 member alkyl that the halogen replaces includes trifluoromethyl, 2- fluoroethyl groups, 2,2,2- trifluoroethyls
In any one.
Optionally, the 3-4 member alkenyl includes allyl；
Optionally, the 3-4 member alkynyl includes propargyl.
Optionally, the 3-6 member naphthenic base includes cyclopropyl, any one in cyclobutyl；
Optionally, the 3-6 member naphthenic base that the halogen replaces includes 2- fluorine cyclopropyl.
Optionally, the corresponding disaccharide of the disaccharide base include maltose, lactose, melibiose, cellobiose, gentiobiose,
Any one in isomaltose.
Optionally, the corresponding monosaccharide of the monosaccharide groups includes galactolipin, glucose acetamide, rhamnose, glucuronic acid.
Optionally, the inorganic acid includes any one in hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid and phosphoric acid.
Optionally, the organic acid includes acetic acid, malonic acid, methanesulfonic acid, succinic acid, p-methyl benzenesulfonic acid, citric acid, rich horse
Acid and any one in malic acid.
The invention also discloses a kind of preparation method of non-glucose carbon glycosides dihydrochalcone, the step of the method
Include:
The preparation of second compound: the first compound, Anhydrous potassium carbonate are dissolved in dry n,N-Dimethylformamide,
Cylite is added in stirring at normal temperature after 30 minutes, react 16 hours at normal temperature, and after thin-layer chromatography monitors fully reacting, distillation is added
Water, be extracted with ethyl acetate three times, merge organic phase, by the organic phase successively wash 3 times, saturated sodium bicarbonate solution wash 1
After secondary, saturated common salt is washed 1 time, it is spin-dried for, column chromatography for separation obtains second compound；First compound is 2,4,6- tri-
Hydroxy acetophenone.
The preparation of third compound: being dissolved in dry tetrahydrofuran for the second compound and obtain the first reaction solution, to
It is slowly added to 60% sodium hydroxide in first reaction solution, after stirring at normal temperature 30 minutes, 4- nitrobenzaldehyde is dissolved in dry
Dry tetrahydrofuran, and be added dropwise in the first reaction solution, thin-layer chromatography monitors after the reaction was completed, distilled water quenching reaction is added,
It is spin-dried for solvent, distilled water dissolution is added, and adjust pH to 4-5 with dilute hydrochloric acid, adds methylene chloride extraction, collect organic phase,
Successively with after distilled water, saturated sodium bicarbonate solution, saturated common salt water washing organic phase, organic phase is concentrated, and is added
Crystal is precipitated in petroleum ether, is slowly stirred under ice-water bath, until filtering after crystal is precipitated completely, dry cake obtains third
Close object.
The preparation of fourth compound: iron powder, ammonium chloride, hydrochloric acid, distilled water being added in bottle with two necks and obtains the second reaction solution,
After second reaction solution is heated to 98 DEG C, by the third compound be dissolved in n,N-Dimethylformamide and be slowly added dropwise to
Second reaction solution, reacts at 98 DEG C, until after the reaction was completed, ethyl acetate and while hot is added in second reaction solution
The organic phase in filtrate is collected in filtering, and successively uses distilled water, saturated sodium bicarbonate solution, saturated common salt water washing organic phase,
It is spin-dried for, obtains fourth compound.
The preparation of 5th compound: the fourth compound, 4-dimethylaminopyridine, pyridine are dissolved in methylene chloride and obtained
Acyl chlorides, acid anhydrides are added dropwise in Xiang Suoshu third reaction solution or replaces organic acid for third reaction solution, and thin-layer chromatography monitors reaction process,
After the reaction was completed, the third reaction solution is successively dissolved in saturated ammonium chloride, saturated sodium bicarbonate solution, distilled water, saturation
Organic phase is collected and be spin-dried for brine It, chromatographs through column and obtains the 5th compound.
The preparation of 6th compound: being dissolved in ethyl acetate and methanol for the 5th compound, by the 5th compound
Quality 30% be added 5% palladium carbon, react in a hydrogen atmosphere, after the reaction was completed, filter, be spin-dried for filtrate obtain the 6th chemical combination
Object.
The preparation of 7th compound: by the 6th compound, disaccharide or monosaccharide in addition to glucose, be dissolved in distilled water with
The mixed liquor of acetonitrile obtains the 4th reaction solution, and trifluoromethanesulfonic acid scandium or trifluoromethanesulfonic acid praseodymium is added in the 4th reaction solution of Xiang Suoshu,
It is heated to reflux, is spin-dried for the 4th reaction solution after the reaction was completed, methanol is added, after solid is precipitated, filter, collect filtrate and be spin-dried for obtaining
Crude product is obtained, column chromatography obtains the 7th compound；7th compound is the non-glucose carbon glycosides dihydrochalcone.
Optionally, the method also includes:
The preparation of salt: the 7th compound is mixed with organic acid or inorganic acid, the 7th compound is made in medicine
Acceptable organic salt or inorganic salts on.
Optionally, the disaccharide includes including maltose, lactose, melibiose, cellobiose, gentiobiose, isomaltose
In any one.
Optionally, the monosaccharide includes galactolipin, glucose acetamide, rhamnose, any one in glucuronic acid.
Optionally, the acyl chlorides includes dimethylaminoethyl chloride.
Optionally, the acid anhydrides include acetic anhydride, it is propionic andydride, butyric anhydride, isobutyric anhydride, any one in trifluoro acid anhydrides
Kind.
Optionally, described that organic acid is replaced to include cyclopropanecarboxylic acid, any one in 2- fluorine cyclopropanecarboxylic acid.
Compared with prior art, the present invention includes the following advantages:
In the embodiment of the present invention, a kind of non-glucose carbon glycosides dihydrochalcone is provided, the A in general formula I is replaced with double
Glycosyl or the monosaccharide groups in addition to glucose can accelerate hypoglycemic onset time, be effectively improved in the case where less toxic side effect
The sugar tolerance of diabetic.
Detailed description of the invention
Fig. 1 is a kind of preparation method flow chart of non-glucose carbon glycosides dihydrochalcone of the embodiment of the present invention；
Fig. 2 is the preparation method flow chart of another non-glucose carbon glycosides dihydrochalcone of the embodiment of the present invention.
Specific embodiment
In order to make the foregoing objectives, features and advantages of the present invention clearer and more comprehensible, with reference to the accompanying drawing and specific real
Applying mode, the present invention is described in further detail.
The present invention provides a kind of non-glucose carbon glycosides dihydrochalcone, the non-glucose carbon glycosides dihydrochalcone is tool
Have the compound of the following general formula I or the non-glucose carbon glycosides dihydrochalcone be compound with the general formula I with it is inorganic
The acceptable salt that acid or organic acid are formed, the salt is as releasing general formula knot under prodrug (prodrug) in vivo physiological condition
Compound shown in structure simultaneously plays pharmacological action as active constituent.
Wherein, in the general formula I, A includes disaccharide base, any one in monosaccharide groups；The monosaccharide groups include removing grape
Monosaccharide groups outside glycosyl；
The substituent group that R is represented includes 1-4 member alkyl, the 3-4 member alkenyl, 3-4 member alkynyl, 3- of 1-4 member alkyl, halogen substitution
6 yuan of naphthenic base, halogen replace 3-6 member naphthenic base in any one.
Term used in the embodiment of the present invention " a-b member alkyl " (a, b are number) refers to the linear chain or branched chain hydrocarbon of saturation
Base has a-b carbon atom, such as 1-6 member alkyl, 1-4 member alkyl.
Optionally, the 1-4 member alkyl be include methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl group, tert-butyl
In any one.Above-mentioned a variety of alkyl are only used for illustrating, other out unlisted alkyl also have similar performance, herein base
It is not repeated them here in length limitation.
Term used in the embodiment of the present invention " a-b member alkenyl " (a, b are number) refers to double containing at least one carbon carbon
The olefinic unsaturation linear chain or branched chain alkyl of key (- C=C-).In the embodiment of the present invention, 3-4 member alkenyl is optionally included.
Optionally, the 3-4 member alkenyl includes allyl.
Term used in the embodiment of the present invention " a-b member alkynyl " (a, b are number) refers to and contains at least one carbon carbon three
The acetylene series unsaturation linear chain or branched chain alkyl of key (- C ≡ C-).In the embodiment of the present invention, 3-4 member alkynyl is optionally included.
Optionally, the 3-4 member alkynyl includes propargyl.Above-mentioned a variety of alkenyls and alkynyl are only used for illustrating, other are not arranged
The alkenyl and alkynyl enumerated also have similar performance, are not repeated them here herein based on length limitation.
Term used in the embodiment of the present invention " a-b member naphthenic base " (a, b are number) means with a-b carbon atom
Saturated cyclic hydrocarbon group.In the embodiment of the present invention, it is optionally 3-6 member naphthenic base.
Optionally, the 3-6 member naphthenic base is cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl.
Above-mentioned a variety of naphthenic base are only used for illustrating, other out unlisted naphthenic base also have similar performance, herein base
It is not repeated them here in length limitation.
Term used in the embodiment of the present invention " halogen " means fluorine, chlorine, bromine or iodine.Optionally, halogen is fluorine.
The alkyl of term used in the embodiment of the present invention " halogen substitution ", the naphthenic base etc. of " halogen substitution ", " halogen takes
In generation ", refers to that compound or group are replaced by one or more halogen atoms.
Optionally, the 1-4 member alkyl that the halogen replaces includes trifluoromethyl, 2- fluoroethyl groups, 2,2,2- trifluoroethyls
In any one.
Optionally, the 3-6 member naphthenic base that the halogen replaces includes 2- fluorine cyclopropyl.
Above-mentioned a variety of substituted compounds are only used for illustrating, in same classification, other out unlisted substituted compounds
With similar performance, do not repeated them here herein based on length limitation.
Term used in the embodiment of the present invention " monosaccharide groups " means former containing 3-6 carbon in molecular structure in addition to glucose
The glycosyl that the sugar of son is formed, that is, include the monosaccharide groups in addition to glucosyl group.
Optionally, the corresponding monosaccharide of the monosaccharide groups includes galactolipin, glucose acetamide, rhamnose, glucuronic acid
In any one.
Term used in the embodiment of the present invention " disaccharide base " means that the sugar formed by two molecule monosaccharide by glycosidic bond is right
The glycosyl answered.
Optionally, the corresponding disaccharide of the disaccharide base include bud sugar, it is lactose, melibiose, cellobiose, gentiobiose, different
Any one in maltose.
Optionally, the inorganic acid includes any one in hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid and phosphoric acid.
Optionally, the organic acid includes acetic acid, malonic acid, methanesulfonic acid, succinic acid, p-methyl benzenesulfonic acid, citric acid, rich horse
Acid and any one in malic acid.
The present invention can also provide a kind of pharmaceutical composition, and the composition may include the compound with aforementioned formula I,
Or the pharmaceutically acceptable salt and pharmaceutically acceptable carrier formed by the compound with aforementioned formula I.This hair
Bright further includes the prodrug of the compounds of this invention, though that is, with certain undocumented structure administration in human body metabolism or conversion
Pharmacological action is played at compound disclosed in the present invention, and as effective component.The preparation conventional method of prodrug is shown in " Design
of Prodrugs》(H.Bundgaad,Elsevier,1985)。
Fig. 1 shows the preparation method flow chart of one of embodiment of the present invention non-glucose carbon glycosides dihydrochalcone,
As shown in Figure 1, specifically, the method for preparing the compound with the general formula I includes:
The preparation of step 101, second compound: the first compound, Anhydrous potassium carbonate are dissolved in dry N, N- dimethyl
In formamide, cylite is added in stirring at normal temperature after 30 minutes, is reacted 16 hours at normal temperature, and thin-layer chromatography monitors fully reacting
Afterwards, distilled water is added, is extracted with ethyl acetate three times, merges organic phase, the organic phase is successively washed into 3 times, unsaturated carbonate
After hydrogen sodium solution washes 1 time, saturated common salt washing 1 time, it is spin-dried for, column chromatography for separation obtains second compound；First compound
For 2,4,6- trihydroxy-acetophenone.
The preparation of step 102, third compound: the second compound is dissolved in dry tetrahydrofuran and obtains first instead
Liquid is answered, 60% sodium hydroxide is slowly added in the first reaction solution of Xiang Suoshu, after stirring at normal temperature 30 minutes, by 4- nitrobenzaldehyde
It is dissolved in dry tetrahydrofuran, and is added dropwise in the first reaction solution, thin-layer chromatography monitors after the reaction was completed, and distilled water quenching is added
Reaction is spin-dried for solvent, distilled water dissolution is added, and adjust pH to 4-5 with dilute hydrochloric acid, adds methylene chloride extraction, collection has
Machine phase is concentrated organic phase successively with after distilled water, saturated sodium bicarbonate solution, saturated common salt water washing organic phase, and
Petroleum ether, which is added, is precipitated crystal, is slowly stirred under ice-water bath, until after crystal is precipitated completely, suction filtration, dry cake obtains the
Three compounds.
The preparation of step 103, fourth compound: iron powder, ammonium chloride, hydrochloric acid, distilled water are added in bottle with two necks and obtains the
The third compound after second reaction solution is heated to 98 DEG C, is dissolved in n,N-Dimethylformamide simultaneously by two reaction solutions
It is slowly added dropwise to second reaction solution, is reacted at 98 DEG C, until after the reaction was completed, acetic acid is added in second reaction solution
Ethyl ester simultaneously filters while hot, collects the organic phase in filtrate, and successively uses distilled water, saturated sodium bicarbonate solution, saturated salt solution
Organic phase is washed, is spin-dried for, obtains fourth compound.
The preparation of step 104, the 5th compound: the fourth compound, 4-dimethylaminopyridine, pyridine are dissolved in dichloro
Methane obtains third reaction solution, and acyl chlorides, acid anhydrides are added dropwise in Xiang Suoshu third reaction solution or replaces organic acid, thin-layer chromatography monitoring is anti-
Process is answered, after the reaction was completed, the third reaction solution is successively dissolved in saturated ammonium chloride, saturated sodium bicarbonate solution, distillation
Water, saturated common salt water washing, collect and are spin-dried for organic phase, chromatograph through column and obtain the 5th compound.
In the embodiment of the present invention, the general formula I R represent substituent group can by using different acyl chlorides, acid anhydrides or
Replace organic acid and obtained using corresponding process for acylating, wherein
Optionally, the acyl chlorides includes dimethylaminoethyl chloride.
Optionally, the acid anhydrides include acetic anhydride, it is propionic andydride, butyric anhydride, isobutyric anhydride, any one in trifluoro acid anhydrides
Kind.
Optionally, described that organic acid is replaced to include cyclopropanecarboxylic acid, any one in 2- fluorine cyclopropanecarboxylic acid.
The preparation of step 105, the 6th compound: being dissolved in ethyl acetate and methanol for the 5th compound, by described
5% palladium carbon is added in the 30% of the quality of five compounds, reacts in a hydrogen atmosphere, after the reaction was completed, filters, is spin-dried for filtrate acquisition
6th compound.
The preparation of step 106, the 7th compound: it by the 6th compound, disaccharide or monosaccharide in addition to glucose, is dissolved in
The mixed liquor of distilled water and acetonitrile obtains the 4th reaction solution, and trifluoromethanesulfonic acid scandium is added in the 4th reaction solution of Xiang Suoshu or, heating
Reflux is spin-dried for the 4th reaction solution after the reaction was completed, and methanol is added, and trifluoromethanesulfonic acid praseodymium after solid is precipitated, and filters, and collects filter
Liquid is spin-dried for obtaining crude product, and column chromatography obtains the 7th compound；7th compound is the non-glucose carbon glycosides dihydro Cha Er
Ketone.
Optionally, the monosaccharide includes galactolipin, glucose acetamide, rhamnose, any one in glucuronic acid.
Optionally, the disaccharide include maltose, lactose, melibiose, cellobiose, gentiobiose, in isomaltose
Any one.
Optionally, the acyl chlorides includes dimethylaminoethyl chloride.
Optionally, the acid anhydrides include acetic anhydride, it is propionic andydride, butyric anhydride, isobutyric anhydride, any one in trifluoro acid anhydrides
Kind.
Optionally, described that organic acid is replaced to include cyclopropanecarboxylic acid, any one in 2- fluorine cyclopropanecarboxylic acid.
Fig. 2 shows the preparation method flow chart of non-glucose carbon glycosides dihydrochalcone another in the embodiment of the present invention,
As shown in Fig. 2, after the step 201-206 identical as above-mentioned steps 101-106, optionally, the method also includes:
The preparation of step 207, salt: the 7th compound is mixed with organic acid or inorganic acid, is made the described 7th and is changed
Close object pharmaceutically acceptable organic salt or inorganic salts.
In order to enable those skilled in the art to better understand the present invention, illustrate the present invention below by way of multiple specific examples
Described in non-glucose carbon glycosides dihydrochalcone preparation method.
Reaction condition: a. trihydroxy-acetophenone, cylite, K2CO3, DMF, room temperature；B.4- nitrobenzaldehyde, 60%NaH,
THF, 0 DEG C-room temperature；C. iron powder, NH4Cl, CuI, 2M HCl, H2O/DMF (1:2), 98 DEG C；D. propionic andydride, pyridine, N, N- diformazan
Aminopyridine (DMAP), CH2Cl2, room temperature；E.5% palladium carbon, H2, methanol/ethyl acetate (2:1)；F. trifluoromethanesulfonic acid praseodymium or three
Fluorine methanesulfonic acid scandium, various disaccharide and monosaccharide in addition to glucose, H2O。
In the embodiment of the present invention, being used herein as English alphabet a, b, c, d ... indicates the condition of every single step reaction, it is subsequent again
When using English alphabet, then it represents that the different glycosyl A connected on non-glucose carbon glycosides dihydrochalcone.
The specific preparation method of the following are the described compound non-glucose carbon glycosides dihydrochalcone with general formula I, wherein
The A of general formula I may is that
The preparation of second compound: by the first compound (2,4,6- trihydroxy-acetophenone) (5.000g,
26.858mmol), Anhydrous potassium carbonate (12.992g, 94.003mmol) is dissolved in the dry n,N-Dimethylformamide DMF of 70mL, often
Cylite (11.160mL, 94.003mmol) is added dropwise after 0.5 hour in temperature stirring, and normal-temperature reaction 16 hours.Thin-layer chromatography TLC prison
Reaction process is controlled, 70mL distilled water is added after fully reacting, afterwards three times with ethyl acetate 70mL extraction, combined ethyl acetate layer.
Ethyl acetate layer is washed with water 3 times respectively, and saturated sodium bicarbonate is washed 1 time, and saturated common salt is washed 1 time, is spin-dried for organic phase.Use 100-
200 mesh silica gel column chromatographies (solvent volume ratio: petroleum ether/dichloromethane/ethyl acetate=32:1:1) colorless oil the
Two compounds, 5.843g (13.325mmol, 49.61%).
The preparation of third compound: the second compound (6.056g, 13.810mmol) is dissolved in 150mL dry four
In hydrogen furans, be slowly added to 60% sodium hydride (1.110g, 27.620mmol) stirring at normal temperature 30 minutes, after by 4- nitrobenzoyl
Aldehyde (2.710g, 17.950mmol) is dissolved in the dry tetrahydrofuran of 50mL, and is added dropwise to reaction system, reaction solution gradually blackening.
Monitor reaction process with TLC, after the reaction was completed, 3mL distilled water quenching reaction be added, after be spin-dried for solvent, 50mL distillation is added
Water, and pH to 4-5 is adjusted with dilute hydrochloric acid, solution becomes bright yellow.The extraction of 50mL methylene chloride is then added, organic layer is used respectively
Water, saturated sodium bicarbonate, saturated common salt water washing.Organic layer is concentrated into 10mL, petroleum ether is added dropwise, solid is precipitated, under ice bath
It is slowly stirred 1h, after crystallization is complete, is filtered, dry cake obtains yellow solid compound 3,7.267g (12.713mmol,
92.06%).
The preparation of fourth compound: iron powder (4.147g, 74.05mmol) is added in 500mL bottle with two necks, ammonium chloride
NH4Cl (396.09mg, 7.405mmol), cuprous iodide CuI (1.407g, 7.405mmol), 2M hydrochloric acid (7.41ml,
14.81mmol), after mixed liquor is heated to 98 DEG C, compound 3 (8.467g, 14.810mmol) is dissolved in for 200mL distilled water
100Ml DMF is slowly added dropwise to reaction system, reacts overnight (generally 12 hours) at 98 DEG C.After the reaction was completed, in body
100mL ethyl acetate is added in system and filters while hot, organic phase uses water, saturated sodium bicarbonate, saturated salt solution respectively in filtrate
Washing is spin-dried for organic phase and obtains yellow solid fourth compound, 7.488g (13.824mmol, 93.34%).
The preparation of 5th compound: by the fourth compound (2.487g, 4.590mmol), 4-dimethylaminopyridine
(DMAP) (1.684g, 13.780mmol), pyridine (1.1mL, 13.780mmol) are dissolved in 30mL methylene chloride, and propionic andydride is added dropwise
(0.710g, 5.508mmol).TLC monitors reaction process, and after the reaction was completed, reaction solution successively uses saturated ammonium chloride, unsaturated carbonate
Hydrogen sodium, water, saturated common salt water washing are spin-dried for organic phase, column chromatography: 100-200 mesh silica gel (solvent volume ratio: dichloromethane
Alkane/petroleum ether/ethyl alcohol=5:5:0.1).Obtain the 5th compound of faint yellow solid, 2.250g (3.764mmol, 82.00%).
The preparation of 6th compound: by the 5th compound (2.25g, 3.76mmol) be dissolved in 5mL ethyl acetate with
10mL methanol is added 5% palladium carbon (0.675g, 30% reactant quality), and reaction is stayed overnight under an atmosphere of hydrogen.After the reaction was completed,
It filters, filtrate is spin-dried for obtaining the 6th compound of white solid, 1.170g (3.552mmol, 94.47%).
The preparation of 7th compound a: by the 6th compound (0.900g, 2.733mmol), D- maltose
(1.721g, 5.029mmol) is dissolved in the mixed solution of 10mL water Yu 10mL acetonitrile, it is rear be added trifluoromethanesulfonic acid scandium (0.269g,
0.547mmol), it is heated to reflux, reacts 24 hours.It is spin-dried for reaction solution after the reaction was completed, methanol is added, be precipitated solid, after suction filtration
Filtrate is taken to be spin-dried for obtaining crude product.Column chromatography, 200-300 mesh silica gel (solvent volume ratio: ethyl acetate/methanol/water=40:2:
1) the 7th compound a of white solid, 52.5mg (0.0803mmol, 2.94%), are obtained.
HRMS(ESI)(M+H)+m/z 654.2399,calcd for C30H40NO15 654.2392.
1H NMR(CD3OD, 700MHz) δ: 7.34 (d, J=8.4Hz, 2H), 7.08 (d, J=8.2 Hz, 2H), 5.12 (d,
J=3.8Hz, 1H), 4.75 (d, J=10.0Hz, 1H), 3.97 (t, J=9.1Hz, 1H), 3.81-3.72 (m, 3H), 3.65-
3.54 (m, 5H), 3.39-3.34 (m, 2H), 3.26-3.22 (m, 1 H), 3.18 (t, J=9.5Hz, 2H), 2.82 (t, J=
7.8Hz, 2H), 2.27 (q, J=7.6Hz, 2H), 1.10 (t, J=7.6Hz, 3H)
13C NMR(CD3OD,176MHz)δ:204.9,204.8,173.9,164.6,164.1,162.8, 137.6,
137.6,136.3,128.4,128.3,120.0,103.9,102.8,101.6,80.0,79.7,78.5, 74.5,73.7,
73.4,72.9,71.2,70.2,61.3,60.6,45.5,30.2,30.2,8.9.
The synthesis of 7th compound b: by the 6th compound (0.400g, 1.214mmol), D- lactose (0.800g,
It 2.338mmol) is dissolved in the mixed solution of 6mL water Yu 6mL acetonitrile, it is rear that trifluoromethanesulfonic acid scandium (0.119g, 0.243mmol) is added,
It is heated to reflux, reacts 24 hours.It is spin-dried for reaction solution after the reaction was completed, methanol is added, solid is precipitated, takes filtrate to be spin-dried for after suction filtration
Crude product.Column chromatography, 200-300 mesh silica gel (solvent volume ratio: ethyl acetate/methanol/water=20:2:1) obtain white solid
Body the 7th compound b, 114.1mg (0.174mmol, 14.38%).
HRMS(ESI)(M+H)+m/z 654.2386,calcd for C30H40NO15 654.2392.
1H NMR(CD3OD, 500MHz) δ: 7.42 (d, J=8.5Hz, 2H), 7.16 (d, J=8.5 Hz, 2H), 5.93 (s,
1H), 4.85 (d, J=11.2Hz, 1H), 4.42 (d, J=7.7Hz, 1H), 4.09 (t, J=9.5Hz, 1H), 3.95-3.68
(m, 6H), 3.63-3.55 (m, 3H), 3.54-3.47 (m, 2H), 3.36-3.31 (m, 2H), 2.90 (t, J=7.7Hz, 2H),
2.36 (q, J=7.6Hz, 2H), 1.18 (t, J=7.6Hz, 3H)
13C NMR(CD3OD,176MHz)δ:205.0,173.9,164.6,163.6,162.6,137.6, 136.3,
128.3,120.1,104.0,103.6,102.7,94.5,79.7,78.9,76.9,75.7,74.4,73.4, 71.3,71.2,
69.0,61.2,60.4,45.6,30.1,29.6,8.9.
The preparation of 7th compound c: by the 6th compound (0.900g, 2.733mmol), D- cellobiose
(1.721g, 5.029mmol) is dissolved in the mixed solution of 10mL water Yu 10mL acetonitrile, it is rear be added trifluoromethanesulfonic acid scandium (0.269g,
0.547mmol), it is heated to reflux, reacts 24 hours.It is spin-dried for reaction solution after the reaction was completed, methanol is added, be precipitated solid, after suction filtration
Filtrate is taken to be spin-dried for obtaining crude product.Column chromatography, 200-300 mesh silica gel (solvent volume ratio: ethyl acetate/methanol/water=40:2:
1) the 7th compound c of white solid, 35.9mg (0.0549mmol, 2.01%), are obtained.
HRMS(ESI)(M-H)-m/z 652.2255,calcd for C30H38NO15 652.2247.
1H NMR(CD3OD, 700MHz) δ: 7.45 (d, J=8.5Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 5.96 (s,
1H), 4.86 (d, J=15.4Hz, 1H), 4.49 (d, J=7.9Hz, 1H), 4.10 (t, J=9.6Hz, 1H), 3.98-3.85
(m, 3H), 3.79-3.67 (m, 2H), 3.36-3.29 (m, 2H), 3.60 (t, J=8.9Hz, 1H), 3.44-3.34 (m, 3H),
3.28(dd,J1=9.2Hz, J2=7.9Hz, 1 H), 2.94 (t, J=8.1Hz, 2H), 2.39 (q, J=7.6Hz, 2H), 1.22
(t, J=7.6Hz, 3H)
13C NMR(CD3OD,176MHz)δ:205.0,204.9,173.9,164.6,163.6,162.6, 137.6,
136.4,128.3,120.0,104.0,103.2,102.8,79.7,78.9,76.9,76.8,76.4,74.4, 73.6,71.3,
69.9,61.0,60.3,45.6,30.2,29.6,8.9.
The preparation of 7th compound d: by the 6th compound (1.200g, 3.644mmol), D- galactolipin
(1.116g, 6.195mmol) is dissolved in the mixed solution of 5mL water Yu 10mL acetonitrile, it is rear be added trifluoromethanesulfonic acid praseodymium (0.358g,
0.729mmol), it is heated to reflux, reacts 24 hours.It is spin-dried for reaction solution after the reaction was completed, methanol is added, be precipitated solid, after suction filtration
Filtrate is taken to be spin-dried for obtaining crude product.Column chromatography, 200-300 mesh silica gel (solvent volume ratio: ethyl acetate/methanol/water=60:2:
1) the 7th compound d of white solid, 53.1mg (0.108mmol, 2.96%), are obtained.
HRMS(ESI)(M+H)+m/z 492.1865,calcd for C24H30NO10 492.1864.
1H NMR(CD3OD+2d D2O, 700MHz) δ: 7.43 (d, J=8.5Hz, 2H), 7.20 (d, J=8.4Hz, 2H),
4.84 (d, J=9.8Hz, 1H), 4.13 (t, J=9.6Hz, 1H), 4.02 (d, J=3.0Hz, 1H), 3.81-3.67 (m, 3H),
3.63(dd,J1=9.4Hz, J2=3.0Hz, 1H), 3.37-3.33 (m, 2H), 2.93 (t, J=7.9Hz, 2H), 2.40 (q, J
=7.6Hz, 2H), 1.21 (t, J=7.6Hz, 3H)
13C NMR(CD3OD,176MHz)δ:204.9,173.9,163.2,137.6,136.3,128.4, 120.0,
104.1,103.5,79.4,75.0,74.9,70.2,69.3,61.5,45.7,30.1,29.6,8.9.
The preparation of 7th compound e: by the 6th compound (0.900g, 2.733mmol), D- melibiose
(1.721g, 5.029mmol) is dissolved in the mixed solution of 10mL water Yu 10mL acetonitrile, it is rear be added trifluoromethanesulfonic acid scandium (0.269g,
0.547mmol), it is heated to reflux, reacts 24 hours.It is spin-dried for reaction solution after the reaction was completed, methanol is added, be precipitated solid, after suction filtration
Filtrate is taken to be spin-dried for obtaining crude product.Column chromatography, 200-300 mesh silica gel (solvent volume ratio: ethyl acetate/methanol/water=30:2:
1) the 7th compound e of white solid, 58.3mg (0.0892mmol, 3.26%), are obtained.
HRMS(ESI)(M-H)-m/z 652.2254,calcd for C30H38NO15 652.2247.
1H NMR(CD3OD+2d D2O, 700MHz) δ: 7.44 (d, J=8.4Hz, 2H), 7.21 (d, J=8.3Hz, 2H),
4.95 (d, J=3.5Hz, 1H), 4.83 (d, J=10.0Hz, 1H), 4.15 (t, J=9.5Hz, 1H), 4.02 (dd, J1=
11.4Hz,J2=4.2Hz, 1H), 3.95-3.88 (m, 2H), 3.82-3.79 (m, 3H), 3.74-3.66 (m, 2H), 3.64-
3.55 (m, 2H), 3.49 (d, J=8.8Hz, 1 H), 3.36-3.29 (m, 2H), 2.92 (t, J=8.1Hz, 2H), 2.41 (q, J
=7.6Hz, 2H), 1.21 (t, J=7.6Hz, 3H)
13C NMR(CD3OD,176MHz)δ:204.90,173.9,164.9,162.6,137.6,136.3, 128.4,
120.0,103.9,102.8,98.9,79.5,78.7,74.7,71.5,70.9,70.2,70.2,69.8, 69.0,66.3,
61.4,45.6,30.2,29.6,8.9.
7th compound f: by the 6th compound (1.200g, 3.644mmol), 2- acetylaminohydroxyphenylarsonic acid D- glucose
(1.370g, 6.195mmol) is dissolved in the mixed solution of 5mL water Yu 10mL acetonitrile, it is rear be added trifluoromethanesulfonic acid praseodymium (0.358g,
0.729mmol), it is heated to reflux, reacts 24 hours.It is spin-dried for reaction solution after the reaction was completed, methanol is added, be precipitated solid, after suction filtration
Filtrate is taken to be spin-dried for obtaining crude product.Column chromatography, 200-300 mesh silica gel (solvent volume ratio: ethyl acetate/methanol/water=60:2:
1) the 7th compound f of white solid, 26.7mg (0.0501mmol, 13.76%), are obtained.
HRMS(ESI)(M+H)+m/z 533.2131,calcd for C26H33N2O10 533.2130.
1H NMR(CD3OD, 700MHz) δ: 7.42 (d, J=8.5Hz, 2H), 7.17 (d, J=8.1 Hz, 2H), 5.86 (s,
1H), 5.48 (d, J=4.3Hz, 1H), 4.92 (d, J=10.2Hz, 1H), 4.64-4.49 (m, 1H), 4.28-4.05 (m,
2H),3.90-3.72(m,3H),3.60-3.48(m,2H), 3.44-3.33(m,2H),2.98-2.86(m,2H),2.36(q,J
=7.6Hz, 2H), 2.04-1.90 (m, 3H), 1.19 (t, J=7.6Hz, 3H)
13C NMR(CD3OD,176MHz)δ:204.9,173.9,171.8,171.6,137.6,136.4, 128.4,
120.0,103.0,102.3,97.6,86.5,86.2,83.4,81.2,78.4,75.8,72.2,71.1, 71.0,70.9,
70.3,62.4,60.8,59.0,29.6,21.2,21.0,8.9.
In the embodiment of the present invention, guaranteeing safety to prove that the non-glucose carbon glycosides dihydrochalcone obtained can obtain
Under implementations, accelerate hypoglycemic onset time, applicant carried out hypoglycemic activity tests:
1) mice group and administration
ICR (Institute of Cancer Research, ICR, american cancer research institute) mouse is purchased from Si Beifu
(Beijing) Bioisystech Co., Ltd, credit number are as follows: SCXK (capital) 2016-0010.Raising is in 12 hours day-night cycles, temperature
22 ± 2 DEG C, in the room of humidity 50 ± 5%, the equal ad lib drinking-water of groups of animals.It is random by weight after adaptive feeding 3 days
Grouping: blank control group (BC:Blank control) positive control drug group (Positive control), experimental group, every group
10.
Feed is maintained to feed mouse, single oral gavage administration with common.0.9% isometric physiology salt of blank control group stomach-filling
Aqueous solvent control, remaining group press the corresponding drug of given dose stomach-filling.
2) general signs are observed
The variation such as excretion, hair color of each group mouse is observed in administration front and back；Measurement weight (is administered according to the weight before administration
Amount), fasting blood-glucose, it is rear to carry out sugar tolerance experiment.
3) blood sugar detection
Mouse Tail-tip is broken with ophthalmologic operation, gently massages mouse tail vein, so that tail point outflow one is bled, discards first
After bleeding, extrusion second, which is bled, to be dripped in test strips, is read.After having surveyed fasting blood-glucose, gastric infusion carries out carbohydrate tolerance test.
4) sugar tolerance experiment (OGTT)
Experiment the previous day whole mouse fasting (can't help water) 12 hours, each group weighed and measured fasting blood-glucose morning next day,
Corresponding drug is given in stomach-filling afterwards, and the physiological saline of isometric(al) is given in blank control, gives mouse 2g/kg body within 1 hour after medicine
The glucose water of weight, 30min, 60min and 120min minutes after glucose water blood glucose values are given in measurement respectively.It is cross with the time
Coordinate, blood glucose value are that ordinate does curve, and area is the sugar tolerance value of mouse under calculated curve.Each group data measured value passes through
Statistics software SPSS17.0 is for statistical analysis.
The influence to normal mouse sugar tolerance is administered in 1 single oral of table
According to upper table data it is found that compared with blank control group, p < 0.001 * p < 0.05, * * p < 0.01, * * *.To sugar
60min after water, the 7th compound f have the function of significant decrease blood glucose level, and the 7th compound c and the 7th compound e also have
Has the tendency that certain reduction blood glucose level；120min, the 7th compound b, the 7th compound c, the 7th chemical combination after to syrup
Object d, the 7th compound e, the 7th compound f all have the ability for significantly reducing blood glucose level.Compared to blank control group,
Seven compound as, the 7th compound b, the 7th compound c, the 7th compound e, the 7th compound f have one on area under the curve
Surely improve trend, wherein the improvement sugar tolerance ability of the 7th compound e is especially pronounced.
Therefore, non-glucose carbon glycosides dihydrochalcone provided by the present application can improve existing while less toxic side effect
There is the hypoglycemic effect of hypoglycemic medicine, accelerate hypoglycemic rate, effectively promotes the sugar tolerance of diabetic.
For embodiment of the method, for simple description, therefore, it is stated as a series of operative combination, but this field
Technical staff should be aware of, and the present invention is not limited by described operation order, because according to the present invention, certain steps can
Sequentially or simultaneously to be carried out using other.Secondly, those skilled in the art should also know that, implementation described in this description
Example belongs to preferred embodiment, and related operation and experiment condition are not necessarily essential to the invention.
Above to a kind of non-glucose carbon glycosides dihydrochalcone provided by the present invention and a kind of non-glucose carbon glycosides two
The preparation method of hydrogen chalcone is described in detail, and specific case used herein is to the principle of the present invention and embodiment
It is expounded, the above description of the embodiment is only used to help understand the method for the present invention and its core ideas；Meanwhile for
Those of ordinary skill in the art have change according to the thought of the present invention in specific embodiments and applications
Place, in conclusion the contents of this specification are not to be construed as limiting the invention.
Claims (10)
1. a kind of non-glucose carbon glycosides dihydrochalcone, which is characterized in that the non-glucose carbon glycosides dihydrochalcone be with
The compound of the following general formula I or the non-glucose carbon glycosides dihydrochalcone are compound and inorganic acid with the general formula I
Or the acceptable salt that organic acid is formed；
Wherein, in the general formula I, A includes disaccharide base, any one in monosaccharide groups；The monosaccharide groups include removing glucosyl group
Outer monosaccharide groups；
The substituent group that R is represented includes 1-4 member alkyl, the 1-4 member alkyl of halogen substitution, 3-4 member alkenyl, 3-4 member alkynyl, 3-6 member
Naphthenic base, halogen replace 3-6 member naphthenic base in any one.
2. non-glucose carbon glycosides dihydrochalcone as described in claim 1, which is characterized in that the 1-4 member alkyl includes first
Base, ethyl, n-propyl, isopropyl, butyl, isobutyl group, any one in tert-butyl；
The 1-4 member alkyl that the halogen replaces includes trifluoromethyl, 2- fluoroethyl groups, any one in 2,2,2- trifluoroethyl
Kind.
3. non-glucose carbon glycosides dihydrochalcone as claimed in claim 2, it is characterised in that:
The 3-4 member alkenyl includes allyl；
The 3-4 member alkynyl includes propargyl.
4. non-glucose carbon glycosides dihydrochalcone as claimed in claim 3, it is characterised in that:
The 3-6 member naphthenic base includes cyclopropyl, any one in cyclobutyl；
The 3-6 member naphthenic base that the halogen replaces includes 2- fluorine cyclopropyl.
5. non-glucose carbon glycosides dihydrochalcone as described in claim 1, it is characterised in that:
The corresponding disaccharide of the disaccharide base include maltose, lactose, melibiose, cellobiose, gentiobiose, in isomaltose
Any one；
The corresponding monosaccharide of the monosaccharide groups includes galactolipin, glucose acetamide, rhamnose, any one in glucuronic acid
Kind.
6. a kind of preparation method of non-glucose carbon glycosides dihydrochalcone as described in any one in claim 1-5, feature exist
In the non-glucose carbon glycosides dihydrochalcone is the compound with the general formula I, which comprises
The preparation of second compound: the first compound, Anhydrous potassium carbonate are dissolved in dry n,N-Dimethylformamide, room temperature
Cylite is added after 30 minutes in stirring, reacts 16 hours at normal temperature, and after thin-layer chromatography monitors fully reacting, distilled water is added,
Be extracted with ethyl acetate three times, merge organic phase, by the organic phase successively wash 3 times, saturated sodium bicarbonate solution wash 1 time,
After saturated common salt is washed 1 time, it is spin-dried for, column chromatography for separation obtains second compound；First compound is 2,4,6- trihydroxy
Acetophenone；
The preparation of third compound: the second compound is dissolved in dry tetrahydrofuran and obtains the first reaction solution, Xiang Suoshu
It is slowly added to 60% sodium hydroxide in first reaction solution, after stirring at normal temperature 30 minutes, 4- nitrobenzaldehyde is dissolved in dry
Tetrahydrofuran, and be added dropwise in the first reaction solution, thin-layer chromatography monitors after the reaction was completed, and distilled water quenching reaction is added, is spin-dried for
Solvent is added distilled water dissolution, and adjusts pH to 4-5 with dilute hydrochloric acid, adds methylene chloride extraction, collects organic phase, successively
After distilled water, saturated sodium bicarbonate solution, saturated common salt water washing organic phase, organic phase is concentrated, and petroleum is added
Crystal is precipitated in ether, is slowly stirred under ice-water bath, until filtering after crystal is precipitated completely, dry cake obtains third chemical combination
Object；
The preparation of fourth compound: iron powder, ammonium chloride, hydrochloric acid, distilled water are added in bottle with two necks and obtains the second reaction solution, by institute
It states after the second reaction solution is heated to 98 DEG C, the third compound is dissolved in n,N-Dimethylformamide and is slowly added dropwise to described
Second reaction solution reacts at 98 DEG C, until after the reaction was completed, ethyl acetate and while hot mistake are added in second reaction solution
The organic phase in filtrate is collected in filter, and successively uses distilled water, saturated sodium bicarbonate solution, saturated common salt water washing organic phase, rotation
It is dry, obtain fourth compound；
The preparation of 5th compound: the fourth compound, 4-dimethylaminopyridine, pyridine are dissolved in methylene chloride and obtain third
Acyl chlorides, acid anhydrides are added dropwise in Xiang Suoshu third reaction solution or replaces organic acid for reaction solution, and thin-layer chromatography monitors reaction process, reaction
After the completion, the third reaction solution is successively dissolved in saturated ammonium chloride, saturated sodium bicarbonate solution, distilled water, saturated common salt
Organic phase is collected and be spin-dried for water washing, chromatographs through column and obtains the 5th compound；
The preparation of 6th compound: being dissolved in ethyl acetate and methanol for the 5th compound, by the matter of the 5th compound
5% palladium carbon is added in the 30% of amount, reacts in a hydrogen atmosphere, after the reaction was completed, filters, is spin-dried for filtrate the 6th compound of acquisition；
The preparation of 7th compound: by the 6th compound, disaccharide or monosaccharide in addition to glucose, it is dissolved in distilled water and acetonitrile
Mixed liquor obtain the 4th reaction solution, trifluoromethanesulfonic acid scandium or trifluoromethanesulfonic acid praseodymium, heating are added in the 4th reaction solution of Xiang Suoshu
Reflux is spin-dried for the 4th reaction solution after the reaction was completed, and methanol is added, and after solid is precipitated, filters, and collection filtrate is spin-dried for obtaining thick
Product, column chromatography obtain the 7th compound；7th compound is the non-glucose carbon glycosides dihydrochalcone.
7. preparation method as claimed in claim 6, which is characterized in that described after the preparation step of the 7th compound
Method further include:
The preparation of salt: the 7th compound is mixed with organic acid or inorganic acid, the 7th compound is made pharmaceutically
Acceptable organic salt or inorganic salts.
8. preparation method as claimed in claims 6 or 7, which is characterized in that the disaccharide include maltose, lactose, melibiose,
Cellobiose, gentiobiose, any one in isomaltose.
9. preparation method as claimed in claims 6 or 7, which is characterized in that the monosaccharide includes galactolipin, glucose acetyl
Amine, rhamnose, any one in glucuronic acid.
10. preparation method as claimed in claims 6 or 7, which is characterized in that the acyl chlorides includes dimethylaminoethyl chloride；
The acid anhydrides includes acetic anhydride, propionic andydride, butyric anhydride, isobutyric anhydride, any one in trifluoro acid anhydrides；
It is described that organic acid is replaced to include cyclopropanecarboxylic acid, any one in 2- fluorine cyclopropanecarboxylic acid.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0598359A1 (en) * | 1992-11-12 | 1994-05-25 | Tanabe Seiyaku Co., Ltd. | Hypoglycemic dihydrochalcone derivatives |
| CN102050852A (en) * | 2009-07-07 | 2011-05-11 | 北京理工亘元医药技术开发中心有限公司 | 2'-O-rhamnosyl swertisin, preparation of analogues thereof, and application thereof |
| CN106496052A (en) * | 2016-10-19 | 2017-03-15 | 汕头大学医学院 | Your ketone compounds a kind of and its preparation method and application |
| CN107686463A (en) * | 2016-08-05 | 2018-02-13 | 安徽中医药大学 | A kind of chalcone aroyl acetyl amines, preparation method and applications |
-
2019
- 2019-04-25 CN CN201910341261.2A patent/CN110078774A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0598359A1 (en) * | 1992-11-12 | 1994-05-25 | Tanabe Seiyaku Co., Ltd. | Hypoglycemic dihydrochalcone derivatives |
| CN102050852A (en) * | 2009-07-07 | 2011-05-11 | 北京理工亘元医药技术开发中心有限公司 | 2'-O-rhamnosyl swertisin, preparation of analogues thereof, and application thereof |
| CN107686463A (en) * | 2016-08-05 | 2018-02-13 | 安徽中医药大学 | A kind of chalcone aroyl acetyl amines, preparation method and applications |
| CN106496052A (en) * | 2016-10-19 | 2017-03-15 | 汕头大学医学院 | Your ketone compounds a kind of and its preparation method and application |
Non-Patent Citations (3)
| Title |
|---|
| ANA R. JESUS，ET AL.: "Targeting Type 2 Diabetes with C-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
| BOOPATHY MANI，ET AL.: "Studies on photocrosslinking and flameretardant properties of chalcone-based polyacrylamides", 《POLYM. ADV. TECHNOL.》 * |
| KHALED H. ALMABRUK，ET AL.: "Total Synthesis of (±)-Isoperbergins and Correction of the Chemical Structure of Perbergin", 《JOURNAL OF NATURAL PRODUCTS》 * |
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