CN1274703C - Unsaturated pyranocarbonoside compounds and preparing process thereof - Google Patents
Unsaturated pyranocarbonoside compounds and preparing process thereof Download PDFInfo
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- CN1274703C CN1274703C CN 02145151 CN02145151A CN1274703C CN 1274703 C CN1274703 C CN 1274703C CN 02145151 CN02145151 CN 02145151 CN 02145151 A CN02145151 A CN 02145151A CN 1274703 C CN1274703 C CN 1274703C
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Abstract
The present invention discloses an unsaturated pyran carbon glucoside compound and a preparation method thereof. The unsaturated pyran carbon glucoside of the present invention has simple and novel structure, and the unsaturated pyran carbon glucoside can be used as an important intermediate body; 1-position, unsaturated groups on saccharide rings and a plurality of reagents can carry out addition reaction so as to achieve the purposes of reforming and modifying saccharide external groups; therefore, the properties of medicines in the aspects of valence, absorption, distribution metabolism, toxicity, stability, solubility, etc. can be changed. Invitro pharmacological activity tests show that the unsaturated pyran carbon glucoside of the present invention has a strong immunological regulation effect, so the unsaturated pyran carbon glucoside has wide application prospect.
Description
Technical field
The present invention relates to class carbon glycoside compound and preparation method thereof, particularly the unsaturated pyrrole of a class is fed the carbon glycoside compound, and the preparation method of this compounds.
Background technology
The carbon glycoside compound extensively is present in occurring in nature, and in separating the natural product that obtains, many carbon glycosides have extraordinary biological activity, is the medicine of the extensive pharmacological action of a class potential tool.
Though carbon glycoside is structurally similar with the nitrogen glucosides to common oxygen glucosides, but because carbon-carbon bond has replaced original hemiacetal, thereby stability is improved greatly, particularly aspect resistance to enzymolysis, thereby be class glycosidase inhibitor of great use, strengthen aspect the human immune system, the vegetable chemistry aspect has a wide range of applications.In the last few years, the develop rapidly of carbon glycoside chemistry, its effect and purposes also constantly development: can be used as the instrument of understanding fully basic biomechanism, also can be used as pharmacological treatment.The carbon glycoside pharmacological action is very extensive: antitumor, antibiotic, antiviral and immunoregulation effect etc. are arranged.Distinctive chemical stability of carbon glycoside and pharmacologically active significantly widely make the chemosynthesis of this compounds and bioactivity research become in recent years important new drug research field in the world; In addition, utilize glycosyl to bring into play the drug effect characteristic in vivo for carrier is easier, can also reduce the toxicity of parent drug greatly, be expected to make the medicine of high-efficiency low-toxicity with this.Therefore, the synthesis and structure transformation of carbon glycoside has become one of focus of current drug research.Quite a few carbon glycoside or its modification show splendid effect clinically at present, and what have is more effective than existing conventional medicine, and side effect is littler.
As document J.Org.Chem.1992,58,3840 have reported a kind of potent antibiotic and transglucosylase (Transglycosylase, the enzyme of saccharan main chain in a kind of synthetic bacterial peptide glycan) inhibitor compound, it has concentrated the feature structure of peptidoglycan and the reactive site of a kind of anti-peptidoglycan main chain polymeric precursor substance moenomycin A (Moenomycin A), and better than the solvability of moenomycin A, act on stronger.Its structural formula is as follows:
Document J.Antibiot.1971,24:558 have reported the bright enzyme element (Triandemycin) that reaches of a kind of new microbiotic-carry.This carbon glycoside compound has very strong restraining effect to the RNA polymerase in the mycetocyte system, and can the interior oxidative phosphorylation process of interference cell.Structural formula is as follows:
As seen, the carbon glycoside with pharmaceutical use of the structure that exploitation is synthetic new has very important realistic meaning, and it can promote Traditional Chinese Medicine industrial expansion and technical progress.
Summary of the invention
One of purpose of the present invention is to disclose a class unsaturated carbon glycoside compounds, because the existence of unsaturated group makes the carbon glycoside compound can be as intermediate and plurality of reagents generation addition reaction, thereby reach the transformation of the outside group of carbon glycoside compound and the purpose of modification, the carbon glycoside class medicine that makes new advances for exploitation provides necessary research basis and foundation.
Two of the object of the invention is to provide the preparation method of a class unsaturated carbon glycoside compounds.
Technical conceive of the present invention is such:
At present, studying the most effective in the main policies of antiviral, antiviral, most active fields is the transformation to glucoside compound, the medicine overwhelming majority that approved is used for anti-various viruses is a glucoside compound, the monomeric configuration part that base, glycosyl and glycosidic link are partly arranged of transforming of glucosides.
Compare with the transformation result of base, will enrich manyly, and the configuration of glycosidic link there is material impact to the biological activity of glucoside compound the forms of modification and the effect of glycosyl and glycosidic link part.In addition, we find in secular study on the synthesis: organo-tin compound is as reaction intermediate or organic synthesis reagent, at some specific type or have the compound of stereochemistry feature and shown unique effect aspect synthetic.For this reason, we have conceived the unsaturated pyrane glycoside compounds that has as next class formation, as:
Formula 1 formula 2
Formula 3 formulas 4
Formula 5
Select allyl group tin compound three normal-butyl allyl group tin (Bu for use
3SnCH
2CH=CH
2) in the sugar ring, form two keys, the compound of glycal glycosides formula 1 and formula 2 structures in obtaining; With three normal-butyl allyl group tin (Bu
3SnCH
2CH=CH
2) outside the sugar ring, introduce diallyl, obtain the compound of more active diene glucosides formula 3 and formula 4 structures; Use organotin hydride tri-n-butyl tin hydrogen ((n-Bu) again
3SnH), obtain the compound of mono-substituted unsaturated glucosides formula 5 structures as reductive agent.The existence of two keys make the carbon glycoside compound can with plurality of reagents generation addition reaction, thereby reach purpose to the transformation and the modification of the outside group of sugar.Our expectation can with this change medicine tire, absorb, the character of aspects such as distribution metabolism, toxicity, stability and solvability, reach orientation and be transported to target tissue, avoid taking place untoward reaction.
The preparation method of compound in turn includes the following steps shown in formula 1 and the formula 2:
(1) unsaturated interior alkene glucoside of allyl group and the unsaturated interior alkene galactoside intermediate of allyl group is synthetic:
With 2; 3; 4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside or 2,3; 4; 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside and Diisopropyl azodicarboxylate (being called for short AIBN, down together) are dissolved in the solvent, and protection of inert gas adds three normal-butyl allyl group tin down; unsaturated interior alkene glucoside of syrup allyl group or the unsaturated interior alkene galactoside of allyl group are collected in infrared lamp irradiation 1-1.5 hour then respectively from reactant.Its reaction formula is:
Said solvent is CH
3CN, CH
3NO
2Or C
6H
6In a kind of, suitable preferred C
6H
6
2; 3; 4; 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside or 2; 3; 4, the mol ratio of 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside, AIBN and three normal-butyl allyl group tin is: 1: (0.1-0.4): (1.5-3.0), preferred proportion is 1: 0.1: 2.6.
(2) deprotection of unsaturated interior alkene glucoside of allyl group and the unsaturated interior alkene galactoside intermediate of allyl group is produced target product:
In the allyl group that step (1) is obtained is unsaturated alkene glucoside or allyl group unsaturated in alkene galactoside (hereinafter to be referred as intermediate) place the reaction that is hydrolyzed of basic solution and alcohols material, obtain target product respectively, promptly 3,4,6-three-hydroxyl-1-allyl group-β-D-1,2 unsaturated glucosides (formula 1) or 3,4,6-three-hydroxyl-1-allyl group-β-D-1,2 unsaturated galactosides (formula 2).Said alcohols material is CH
3OH or CH
3CH
2OH or their mixture, suitable preferred CH
3OH.Said basic solution is CH
3The methanol solution of ONa or triethylamine aqueous solution, the triethylamine concentration of volume percent is preferably 10%.Reaction formula is as follows:
The processing condition of reaction are:
Stirred 30-50 minute under the room temperature, the mol ratio of intermediate and alcohols is 1: (5-8).
Compounds process for production thereof shown in formula 3 and the formula 4 in turn includes the following steps:
(1) diallyl glucoside and diallyl galactoside intermediate is synthetic
With 2; 3; 4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside or 2,3; 4; 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside and AIBN are dissolved in the solvent, add three normal-butyl allyl group tin under protection of inert gas, infrared lamp irradiation 1-2.5 hour; collect syrup diallyl glucoside or diallyl galactoside then respectively from reactant, its reaction formula is:
Said solvent is CH
3CN, CH
3NO
2Or C
6H
6In a kind of, suitable preferred C
6H
6
2; 3; 4; 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside or 2; 3; 4, the mol ratio of 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside, AIBN and three normal-butyl allyl group tin is: 1: (0.1-0.4): (3.0-5.5), preferred proportion is: 1: 0.1: 5.0.
(2) deprotection of diallyl glucoside and diallyl galactoside intermediate (hereinafter to be referred as intermediate) is produced target product:
Diallyl glucoside that step (1) is obtained or diallyl galactoside place the reaction that is hydrolyzed of basic solution and alcohols material, obtain target product respectively, promptly 2,3,4,6-four-hydroxyl-1,1 '-diallyl-β-D-glucoside (formula 3) or 2,3,4,6-four-hydroxyl-1,1 '-diallyl-β-D-galactoside (formula 4).Said alcohols material is CH
3OH or CH
3CH
2OH or their mixture, suitable preferred CH
3OH.Said basic solution is CH
3The methanol solution of ONa or triethylamine aqueous solution, the triethylamine concentration of volume percent is preferably 10%.Reaction formula is as follows:
The processing condition of reaction are:
Stirred 2-4 hour under the room temperature, the mol ratio of intermediate and alcohols is 1: (5-8).
Compounds process for production thereof shown in the formula 5 in turn includes the following steps:
(1) allyl group galactoside intermediate is synthetic:
With 2,3,4; 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside and AIBN are dissolved in the solvent, add tri-n-butyl tin hydrogen under protection of inert gas in batches, infrared lamp irradiation 2-3.5 hour; collect syrup allyl group galactoside then from reactant, its reaction formula is:
Said solvent is CH
3CN, CH
3NO
2Or C
6H
6In a kind of, suitable preferred C
6H
6
2,3,4, the mol ratio of 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside, AIBN and tri-n-butyl tin hydrogen is: 1: (0.1-0.4): (3.5-6.5), preferred proportion is: 1: 0.1: 6.5.
(2) deprotection of allyl group galactoside intermediate is produced target product:
The allyl group galactoside (hereinafter to be referred as intermediate) that step (1) is obtained places the reaction that is hydrolyzed of basic solution and alcohols material, obtains target product, and promptly 2,3,4,6-four-hydroxyl-1-allyl group-β-D-galactoside (formula 5).Said alcohols material is CH
3OH or CH
3CH
2OH or their mixture, suitable preferred CH
3OH.Said basic solution is CH
3The methanol solution of ONa or triethylamine aqueous solution, the triethylamine concentration of volume percent is preferably 10%.Reaction formula is as follows:
The processing condition of reaction are:
Stirred under the room temperature 7-10 hour, the mol ratio of intermediate and alcohols is 1: (5-8).
The unsaturated pyrane glucosides novelty not only simple in structure of indication of the present invention, and can be used as the important intermediate of a class, unsaturated group on 1-position and the sugar ring can with plurality of reagents generation addition reaction, thereby reach purpose to the transformation and the modification of the outside group of sugar, and with this change medicine tire, absorb, the character of aspect such as distribution metabolism, toxicity stability and solvability, reach orientation and be transported to target tissue, avoid taking place untoward reaction.Through external pharmacologically active test, unsaturated pyrane glucosides of the present invention has stronger immunoregulation effect, thereby has very wide application prospect.
Embodiment
Below with reference to embodiment related content of the present invention is further illustrated, but these embodiment do not limit protection scope of the present invention.
Embodiment 1
Synthesizing of compound shown in the formula 1:
With 140mg compound 2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside and 10mgAIBN are dissolved in the benzene, add 250mg three normal-butyl allyl group tin.Under the argon shield, 250W infrared lamp irradiation 1 hour adds the 700mg Potassium monofluoride then; 0.84ml water, the 3.9ml acetonitrile stirs after-filtration and removes inorganic salt; the decompression rotary evaporation is removed solvent; column chromatography gradient elution on the enriched material, elutriant are sherwood oil: ethyl acetate=5.5: 1,5: 1; 4: 1; obtain the unsaturated interior alkene glucoside of 71mg syrup allyl group, productive rate 66%, stand-by.
Get the allyl group that obtains by above-mentioned experiment unsaturated in alkene glucoside 30mg be dissolved in that (0.1N is in the methanol solution of sodium methylate 7.8ml).Stirred hydrolysis reaction 40 minutes, the pressure reducing and steaming solvent, column chromatography ethyl acetate on the enriched material: ethanol: sherwood oil=10: 5: 20,10: 5: 18,10: 5: 16 mixed solvent wash-outs, after the gained elutriant reduced pressure and removes mixed solvent, promptly obtaining the filbert syrup of 16.1mg was compound shown in the formula 1, productive rate 91%.
Formula 1 compound analysis test data is as follows:
Rf=0.45 (ethyl acetate: ethanol: sherwood oil=10: 5: 12)
[α]
D 20＝+25.8(c＝0.345，MeOH)
1HNMR(500.130MHz，CDCl
3)：δ＝5.80(ddt，1H，J
2，1＝10.2Hz，J
2，1’＝16.9Hz，J
2，3＝J
2，3’＝6.5Hz，H-2)，5.08(dd，1H，H-1)，5.04(d，1H，H-1’)，4.57(d，1H，J
5，6＝2.4Hz，H-5)，4.11(dd，1H，J
6，7＝1.2Hz，J
7，8＝6.0Hz，H-7)，3.84～3.77(m，3H，H-6，H-9，H-8)，3.56(dd，1H，J
9，9’＝9.0Hz，J
8，9’＝6.8Hz，H-9’)，2.75(d，2H，H-3，H-3’)。
MS(EI)：m/z?186[M]
+113[M-CH
2CH＝CH
2-CH
3OH]
+
This compound is 10 in concentration
-5Mol/L, 10
-6Mol/L, 10
-7During mol/L, T lymphocyte inhibiting rate is reached 51%, 37%, 19% respectively, the bone-marrow-derived lymphocyte inhibiting rate is reached 12%, 12%, 10% respectively.Anti-general bacterium and anti-diabetic activity are not obvious.
Compound is the same shown in the synthetic method cotype 1 of compound shown in the formula 2, is white solid, productive rate 93%.
Formula 2 compound analysis test datas are as follows:
Rf=0.39 (chloroform: methyl alcohol: sherwood oil=10: 2: 2)
[α]
D 20＝+17.9(c＝0.525，MeOH)
1H?NMR(500.130MHz，CDCl
3)：δ＝5.81(ddt，1H，J
2，1＝10.2Hz，J
2，1’＝16.9Hz，J
2，3＝J
2，3’＝6.6Hz，H-2)，5.07(dd，1H，H-1)，5.02(dd，1H，H-1’)4.45(s，1H，H-5)，4.36(d，1H，J
5，6＝1.6Hz，H-6)，3.95(dd，1H，J
6，7＝4.6Hz，J
7，8＝7.9Hz，H-7)，3.82(d，1H，H-8)，3.75(dd，1H，J
9，9’＝11.8Hz，J
8，9＝7.9Hz，H-9)，3.68(dd，1H，J
8，9’＝4.7Hz，H-9’)，2.73(d，2H，H-3，H-3’)。
MS(EI)：m/z?186[M]
+ 113[M-CH
2CH＝CH
2-CH
3OH]
+
This compound is 10 in concentration
-5Mol/L, 10
-6Mol/L, 10
-7During mol/L, T lymphocyte inhibiting rate is reached 41%, 23%, 12% respectively, the bone-marrow-derived lymphocyte inhibiting rate is reached 2%, 11%, 22% respectively.Anti-general bacterium and anti-diabetic activity are not obvious.
Embodiment 2
Synthesizing of compound shown in the formula 3:
With 46mg compound 2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside and 3mgAIBN are dissolved in the benzene, add 186mg three normal-butyl allyl group tin.Under the argon shield, 250W infrared lamp irradiation 1.5 hours adds the 360mg Potassium monofluoride then; 0.228ml water, the 2.03ml acetonitrile stirs after-filtration and removes inorganic salt; the filtrate decompression rotary evaporation is removed solvent; column chromatography gradient elution on the enriched material, elutriant are sherwood oil: ethyl acetate=5: 1,4: 1; 3: 1; obtain 18.3mg syrup diallyl glucoside, productive rate 38.9%, stand-by.
Get the diallyl glucoside 30mg that obtains by above-mentioned experiment and be dissolved in that (0.1N is in the methanol solution of sodium methylate 4ml).Stir hydrolysis reaction after 3 hours, behind the pressure reducing and steaming solvent, the enriched material rapid column chromatography, use methylene dichloride: methyl alcohol=22: 2,20: 2,18: 2 mixed solvent wash-outs, the elutriant of collection is after concentrating under reduced pressure is removed mixed solvent, obtaining the 17.3mg white solid is compound shown in the formula 3, productive rate 98%.
Formula 3 compound analysis test datas are as follows:
Rf=0.44, methylene dichloride: methyl alcohol=20: 2; Polarimetry is dextrorotation
1H?NMR(500.130MHz，CDCl
3)：δ＝5.83(m，2H，H-2，H-2’)，5.10(dd，4H，H-1a，H-1b，H-1’a，H-1’b)，3.73(d，1H，H-6)，3.61(m，2H，H-5，H-7)，3.49(dd，1H，J
9，8＝3.8Hz，J
9，9’＝9.8Hz，H-9)，3.43(d，1H，H-9’)，3.23(t，1H，H-8)，2.58(dd，1H，J
1’a，2’＝6.6Hz，J
3’a，3’b＝15.1Hz，H-3’a)，2.42(dd，1H，J
3a，2＝5.6Hz，J
3a，3b＝14.8Hz，H-3a)，2.27(dd，1H，J
3’b，2’＝8.8Hz，H-3’b)，2.19(dd，1H，J
3b，2＝7.7Hz，H-3b)。
MS(EI)：m/z?245[M+1]
+203[M-CH
2CH＝CH
2]
+185[M-CH
2CH＝CH
2-H
2O]
+
This compound is 10 in concentration
-5Mol/L, 10
-6Mol/L, 10
-7During mol/L, T lymphocyte inhibiting rate is reached 23%, 18%, 25% respectively, the bone-marrow-derived lymphocyte inhibiting rate is reached 18%, 22%, 15% respectively.Anti-general bacterium and anti-diabetic activity are not obvious.
Compound is the same shown in the synthetic cotype 3 of compound shown in the formula 4, is white solid, productive rate 97%.
Formula 4 compound analysis test datas are as follows:
Rf=0.42, methylene dichloride: methyl alcohol=20: 2; Polarimetry is dextrorotation
1H?NMR(500.130MHz，CDCl
3)：δ＝5.82(m，2H，H-2，H-2’)，5.06(m，4H，H-1a，H-1b，H-1’a，H-1’b)，3.84(d，1H，J
6，7＝2.5Hz，J
7，8＝0.8Hz，H-7)，3.75～3.68(m，3H，H-5，H-6，H-9)，3.55(m，2H，H-8，H-9’)，2.57(dd，1H，J
1’a，2’＝6.7Hz，J
3’a，3’b＝15.0Hz，H-3’a)，2.37(dd，1H，J
3a，2＝5.9Hz，J
3a，3b＝14.8Hz，H-3a)，2.26(dd，1H，J
3’b，2’＝8.8Hz，H-3’b)，2.13(dd，1H，J
3b，2＝7.6Hz，H-3b)。
MS(EI)：m/z?245[M+1]
+203[M-CH
2CH＝CH
2]
+185[M-CH
2CH＝CH
2-H
2O]
+
This compound is 10 in concentration
-5Mol/L, 10
-6Mol/L, 10
-7During mol/L, T lymphocyte inhibiting rate is reached 39%, 43%, 42% respectively, bone-marrow-derived lymphocyte is reached 8% (inhibiting rate), 8% (enhancing rate), 10% (enhancing rate) respectively.Anti-general bacterium and anti-diabetic activity are not obvious.
Embodiment 3
About 2,3,4,6-four-hydroxyl-1-allyl group-β-D-glucoside compound synthetic:
With 46mg compound 2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside and 3mgAIBN are dissolved in the 8ml benzene, add 94.1mg tri-n-butyl tin hydrogen.Under the argon shield; 250W infrared lamp irradiation 55 minutes; add 78mg tri-n-butyl tin hydrogen again; shone 80 minutes; the cooling back adds the 311.5mg Potassium monofluoride; 0.31ml water, the 1.25ml acetonitrile stirs after-filtration and removes inorganic salt; filtrate decompression rotary evaporation is then removed solvent; the column chromatography gradient elution is used sherwood oil: ethyl acetate=5.5: 1,5: 1 mixed solvent wash-outs; the elutriant of collecting is after concentrating under reduced pressure is removed mixed solvent; obtain 15.6mg allyl group glucoside syrup, productive rate 37%, stand-by.
Get in the mixing solutions (5mL) of the distilled methyl alcohol-triethylamine of difference-water that the allyl group glucoside 24mg that obtains by above-mentioned experiment is dissolved in 8: 1: 1.Stirred hydrolysis reaction 10 hours, the pressure reducing and steaming solvent, column chromatography on the enriched material, use ethyl acetate: ethanol: sherwood oil=10: 2: 3, mixed solvent carried out gradient elution in 10: 2: 2, the elutriant of gained is after concentrating under reduced pressure is removed mixed solvent, obtain the yellow syrup 1 of 12.7mg and be above-mentioned 2,3,4,6-four-hydroxyl-1-allyl group-β-D-glucoside compound, productive rate 97%.
Above-mentioned said compound analysis test data is as follows:
Rf=0.41 (ethyl acetate: ethanol: sherwood oil=10: 2: 1.5); Polarimetry is dextrorotation
1HNMR(500.130MHz，CDCl
3)：δ＝5.85(ddt，1H，J
2，1＝10.3Hz，J
2，1’＝16.9Hz，J
2，3＝J
2，3’＝6.6Hz，H-2)，5.07(dd，2H，H-1，H-1’)，3.78(dd，1H，J
5，6＝10.6Hz，H-6)，3.56(dd，1H，J
6，7＝5.6Hz，J
7，8＝12.3Hz，H-7)，3.37～3.25(m，4H，H-5，H-9，H-9’，H-8)，3.14(m，1H，H-4)，2.53(m，1H，H-3)，2.18(m，1H，H-3’)。
MS(EI)：m/z?205[M+1]
+163[M-CH
2CH＝CH
2]
+146[M-CH
2CH＝CH
2-OH]
+
This compound is 10 in concentration
-5Mol/L, 10
-6Mol/L, 10
-7During mol/L, T lymphocyte inhibiting rate is reached 39%, 34%, 42% respectively, bone-marrow-derived lymphocyte enhancing rate is reached 21%, 20%, 22% respectively.Anti-general bacterium and anti-diabetic activity are not obvious.
The synthetic method of compound shown in the formula 5 is the same with compound shown in above-mentioned, but the gained compound is a white solid, productive rate 97%.
Formula 5 compound analysis test datas are as follows:
Rf=0.24, methylene dichloride: methyl alcohol=16: 2; Polarimetry is dextrorotation
1H?NMR(500.130MHz，CDCl
3)：δ＝5.82(ddt，1H，J
2，1＝10.3Hz，J
2，1’＝17.3Hz，J
2，3＝J
2，3’＝6.6Hz，H-2)，5.05(dd，2H，H-1)，4.99(d，1H，H-1’)，3.81(d，1H，H-7)，3.59(dd，1H，J
5，4＝7.9Hz，J
5，6＝11.7Hz，H-5)，3.55(dd，1H，J
6，7＝4.4Hz，H-6)，3.48(dd，1H，J
9，8＝3.5Hz，H-9)，3.45(dd，1H，J
8，9’＝3.5Hz，J
9，9’＝9.1Hz，H-9’)，3.34(t，1H，H-8)，3.20(dt，1H，H-4)，2.49(m，1H，H-3)，2.15(m，1H，H-3’)。
MS(EI)：m/z?205[M+1]
+162[M-CH
3CH＝CH
2]
+145[M-CH
2CH＝CH
2-H
2O]
+
This compound is 10 in concentration
-5Mol/L, 10
-6Mol/Ll, 10
-7During mol/L, T lymphocyte inhibiting rate is reached 31%, 38%, 26% respectively, bone-marrow-derived lymphocyte enhancing rate is reached 5%, 15%, 14% respectively.Anti-general bacterium and anti-diabetic activity are not obvious.
Claims (4)
1. the unsaturated pyrane glycoside compounds of a class, its feature structure formula is as follows:
Formula 1 formula 2
Formula 3 formulas 4
Formula 5
2. the preparation method of compound as claimed in claim 1 is characterized in that having formula 1, the compound its preparation method of formula 2 structural formulas in turn includes the following steps:
(1) unsaturated interior alkene glucoside of allyl group or the unsaturated interior alkene galactoside intermediate of allyl group is synthetic:
With 2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside or 2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside and AIBN are dissolved in the solvent, under protection of inert gas, add three normal-butyl allyl group tin, unsaturated interior alkene glucoside of syrup allyl group or the unsaturated interior alkene galactoside of allyl group are collected in infrared lamp irradiation 1-1.5 hour then respectively from reactant; Said solvent is CH
3CN, CH
3NO
2Or C
6H
6In a kind of;
2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside or 2,3,4, the mol ratio of 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside, AIBN and three normal-butyl allyl group tin is: 1: (0.1-0.4): (1.5-3.0);
(2) deprotection of unsaturated interior alkene glucoside of allyl group or the unsaturated interior alkene galactoside intermediate of allyl group is produced target product:
In the allyl group that step (1) is obtained is unsaturated alkene glucoside or allyl group unsaturated in alkene galactoside intermediate place the reaction that is hydrolyzed of basic solution and alcohols material, obtain target product respectively, promptly 3,4,6-three-hydroxyl-1-allyl group-β-D-1,2 unsaturated glucosides (formula 1) or 3,4,6-three-hydroxyl-1-allyl group-β-D-1,2 unsaturated galactosides (formula 2); Wherein said basic solution is CH
3The methanol solution of ONa or triethylamine aqueous solution, said alcohols material are CH
3OH or CH
3CH
2OH or their mixture;
The processing condition of reaction are: stirred 30-50 minute under the room temperature, the mol ratio of unsaturated interior alkene galactoside intermediate of alkene glucoside or allyl group and alcohols was 1 in allyl group was unsaturated: (5-8).
3. the preparation method of compound as claimed in claim 1 is characterized in that having formula 3, the compound its preparation method of formula 4 structural formulas in turn includes the following steps:
(1) diallyl glucoside or diallyl galactoside intermediate is synthetic
With 2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside or 2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside and AIBN are dissolved in the solvent, under protection of inert gas, add three normal-butyl allyl group tin, syrup diallyl glucoside or diallyl galactoside are collected in infrared lamp irradiation 1-2.5 hour then respectively from reactant; Said solvent is CH
3CN, CH
3NO
2Or C
6H
6In a kind of;
2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-glucoside or 2,3,4, the mol ratio of 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside, AIBN and three normal-butyl allyl group tin is: 1: (0.1-0.4): (3.0-5.5);
(2) deprotection of diallyl glucoside or diallyl galactoside intermediate is produced target product:
Diallyl glucoside that step (1) is obtained or diallyl galactoside intermediate place the reaction that is hydrolyzed of basic solution and alcohols material, obtain target product respectively, promptly 2,3,4,6-four-hydroxyl-1,1 '-diallyl-β-D-glucoside (formula 3) or 2,3,4,6-four-hydroxyl-1,1 '-diallyl-β-D-galactoside (formula 4); Wherein said basic solution is CH
3The methanol solution of ONa or triethylamine aqueous solution, said alcohols material are CH
3OH or CH
3CH
2OH or their mixture;
The processing condition of reaction are: stirred 2-4 hour under the room temperature, the mol ratio of above-mentioned intermediate and alcohols is 1: (5-8).
4, the preparation method of compound as claimed in claim 1 is characterized in that the compound its preparation method with formula 5 structural formulas in turn includes the following steps:
(1) allyl group galactoside intermediate is synthetic:
With 2,3,4,6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside and AIBN are dissolved in the solvent, add tri-n-butyl tin hydrogen in batches, and syrup allyl group galactoside is collected in infrared lamp irradiation 2-3.5 hour then from reactant; Said solvent is CH
3CN, CH
3NO
2Or C
6H
6In a kind of; 2,3,4, the mol ratio of 6-four-O-ethanoyl-1-chloro-1 '-allyl group-β-D-galactoside, AIBN and tri-n-butyl tin hydrogen is: 1: (0.1-0.4): (3.5-6.5);
(2) deprotection of allyl group galactoside intermediate is produced target product:
The allyl group galactoside that step (1) is obtained places the reaction that is hydrolyzed of basic solution and alcohols material, obtains target product, and promptly 2,3,4,6-four-hydroxyl-1-allyl group-β-D-galactoside (formula 5); Wherein said basic solution is CH
3The methanol solution of ONa or triethylamine aqueous solution, said alcohols material are CH
3OH or CH
3CH
2OH or their mixture; The processing condition of reaction are: stirred under the room temperature 7-10 hour, the mol ratio of above-mentioned intermediate and alcohols is 1: (5-8).
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