CN1699356A

CN1699356A - Benzo-dihydropyran glycoside derivatives

Info

Publication number: CN1699356A
Application number: CN 200510026377
Authority: CN
Inventors: 陈国荣; 何立; 让·皮埃尔·普拉利
Original assignee: East China University of Science and Technology
Current assignee: East China University of Science and Technology
Priority date: 2005-06-01
Filing date: 2005-06-01
Publication date: 2005-11-23
Anticipated expiration: 2025-06-01
Also published as: CN100334080C

Abstract

The invention relates to a benzo-dihydropyran glycoside derivatives whose structure is illustrated by formula (I) disclosed in the specification, the derivative is prepared through using corresponding hydroquinone or hydroxybenzene as starting raw material, then carrying out methylation, 1,2,3,4,substitution of phenyl ring by 6-penta-O-acetyl-beta-D-glucopyranose, benzene quinonization, hydrogen quinonization, cyclisation and alcoholysis. In formula (I), R1, R3 are selected from H, CH3 and one of (II), R2 is C1-C16 alkyl, R4 is H or CH3, wherein at least one of R1 and R3 is (III) but R1 and R3 cannot be (IV) at the same time.

Description

Benzo-dihydropyran glycoside derivatives

Technical field

The present invention relates to a kind of benzo-dihydropyran glycoside derivatives.

Background technology

Tocopherols compound (vitamin-E) is the important compound of a class in the chroman derivatives, vitamin-E is as antioxidant the most outstanding in the organism and radical scavenger, medicine, food, feed have been widely used in, in the related industries such as makeup and material.

Yet, thereby limit its application because vitamin-E or its analogue is water-soluble very poor.Thereby it is water-soluble to improve it to introduce hydrophilic radical on vitamin-E, thereby obtains the amphiphatic vitamin-E of hydrophilic lipophilic tool, can promote the application that it is more wide greatly.Document Carbohydrate Research, 23,299,1997 and 72,325,2000 reports, with glucose or its oligosaccharides and vitamin-E direct synthesising complex E grape glycosyloxy glucosides under the catalysis of Lewis acid, its structure is as follows respectively:

N is an integer between the 0-6

Yet because the phenolic hydroxyl group on the vitamin-E parent chroman ring is most important to anti-oxidant activity, the destruction phenolic hydroxyl group just makes vitamin-E reduce greatly or loses anti-oxidant activity.The structure of above-mentioned bibliographical information has been just owing to destroyed hydroxyl on the chroman ring, thereby caused the low activity of these structures.In addition, the direct glucosides meeting of vitamin-E causes vitamin-E very easily oxidized, generates the oxidized byproduct of a series of following structures, thereby causes the reduction of productive rate.

R=OH，Et

Therefore, how keeping under chroman derivatives (tocopherols compound or its analogue) the anti-oxidant activity prerequisite, increasing it and water-solublely just become the technical issues that need to address of the present invention.

Summary of the invention

The present invention introduces pyranoglucose and obtains a class benzo-dihydropyran glycoside derivatives on the phenyl ring of the parent chroman of tocopherols compound or its analogue.Experiment shows, the water-soluble obvious enhancing of this analog derivative.In addition, because pyranoglucose is to be substituted on the phenyl ring but not on the phenolic hydroxyl group, therefore to have kept the anti-oxidant activity of this analog derivative preferably.

The said benzo-dihydropyran glycoside derivatives of the present invention has following structure:

In the formula: R ₁, R ₃Be selected from H respectively, CH ₃With

In a kind of; R ₂Be C ₁-C ₁₆Alkyl; R ₄Be H or CH ₃

Wherein: R ₁And R ₃In at least one is , but R ₁And R ₃Be not simultaneously

In the present invention, preferred R ₂Be C ₁-C ₁₆Chain (straight chain or have side chain) alkyl; Best R ₂Be CH ₃Or

The preparation method of the said benzo-dihydropyran glycoside derivatives of the present invention is: with corresponding Resorcinol (quinhydrones) or corresponding phenol is starting raw material; successively through methylate (for phenyl ring), 1; 2; 3; 4,6-five-0-ethanoyl-β-D-pyranoglucose after to replacement, benzoquinonesization, quinhydronesization, cyclisation and the alcoholysis of phenyl ring target compound.As with 2,3-dimethyl hydroquinone or 2,6-xylenol are that the preparation method of starting raw material comprises the steps:

(1) 1,4-is to methoxyl group-2, and 3-dimethyl benzene and 1,4-be to methoxyl group-2,6-dimethyl benzene synthetic:

A) 1,4-is to methoxyl group-2,3-dimethyl benzene synthetic:

With 2, the 3-dimethyl hydroquinone is dissolved in the dimethyl sulfoxide (DMSO), stir to add methyl iodide and potassium hydroxide solid down, and room temperature reaction 4～5 hours, reaction product obtains 1 behind extraction, washing, drying and column chromatography, and 4-is to methoxyl group-2,3-dimethyl benzene (white crystals); Reaction formula is:

Wherein, 2, the mol ratio of 3-dimethyl hydroquinone, methyl iodide, potassium hydroxide is 1: (3～5): (2～4).

B) 1,4-is to methoxyl group-2,6-dimethyl benzene synthetic:

With freshly prepd Fermi's salt (Fremy ' s salt) 0 ℃ soluble in water down, in this aqueous solution, add 2, the methanol solution of 6-xylenol.Reacted under the room temperature 6～8 hours, reaction product obtains yellow crystal 2,6-phlorone after extraction, washing, drying.With obtain 2, the 6-phlorone is dissolved in the chloroform, the powder that takes a policy (Sodium Hydrosulphite, Na ₂S ₂O ₄) the aqueous solution, vigorous stirring is 10～20 minutes under the room temperature, reaction product is removed chloroform through concentrating, and obtains white solid 2 after extracted with diethyl ether, washing, drying, the 6-dimethyl hydroquinone.With 2, the 6-dimethyl hydroquinone is dissolved in the dimethyl sulfoxide (DMSO) again, and adds methyl iodide and potassium hydroxide solid, room temperature reaction 4～5 hours, reaction product behind extraction, washing, drying and column chromatography 1,4-is to methoxyl group-2,6-dimethyl benzene (light yellow oil liquid); Its reaction formula is as follows:

Wherein, 2,6-phlorone, Na ₂S ₂O ₄Mol ratio be 1: (2～5), 2, the mol ratio of 6-dimethyl hydroquinone, methyl iodide, potassium hydroxide is: 1: (3～5): (2～4).

(2) 1-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,5-dimethoxy-3,4-dimethyl benzene and 1-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,4-dimethyl-3,6-dimethoxy benzene synthetic:

With 1,2,3,4,6-five-0-ethanoyl-β-D-pyranoglucose respectively with by institute's synthetic 1 in the step (1), 4-is to methoxyl group-2,3-dimethyl benzene and 1,4-are to methoxyl group-2, the 6-dimethyl benzene is dissolved in CH ₂Cl ₂In, stir and drop into catalyzer trifluoroacetic acid silver (AgOTfa) down earlier, add SnCl again ₄CH ₂Cl ₂Solution.System's lucifuge charges into argon shield, and reaction is 2-4 hour under 20-30 ℃ condition, reaction product is carried out recrystallization through extraction with after column chromatography for separation removes inorganics and other organic by-products in mixed solvent, respectively must 1-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,5-dimethoxy-3,4-dimethyl benzene (white crystal) and 1-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,4-dimethyl-3,6-dimethoxy benzene (white foam); Its reaction formula is as follows:

Wherein, 1,2,3,4,6-five-0-ethanoyl-β-D-pyranoglucose and 1,4-be to methoxyl group-2, and 3-dimethyl benzene or 1,4-be to methoxyl group-2,6-dimethyl benzene, AgOTfa and SnCl ₄Mol ratio be 1: (1.5-2): (1.0-1.6): (1.5-2.4); Temperature of reaction is 20-30 ℃; The used mixed solvent of recrystallization is ether and sherwood oil mixture, and its volume ratio is 1: 2.(3) 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl-1,4-benzoquinones and 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl-1,4-benzoquinones synthetic:

Will be by the synthetic 1-of institute (2 in the step (2); 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2; 5-dimethoxy-3; 4-dimethyl benzene and 1-(2,3,4; 6-four-0-ethanoyl-β-D-pyranoglucose)-2; 4-dimethyl-3,6-dimethoxy benzene are dissolved in respectively in the acetonitrile, drip cerous ammonium nitrate ((NH under the room temperature ₄) ₂Ce (NO ₃) ₆, stirred 20-40 minute, obtain 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2 respectively, 3-dimethyl-1,4-benzoquinones and 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl-1,4-benzoquinones.Reaction formula is as follows:

Wherein, 1-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,5-dimethoxy-3,4-dimethyl benzene or 1-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,4-dimethyl-3, the mol ratio of 6-dimethoxy benzene and cerous ammonium nitrate is 1: (3-5);

(4) 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl hydroquinone and 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl hydroquinone synthetic:

Will be by the synthetic 5-of institute (2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2 in the step (3); 3-dimethyl-1,4-benzoquinones and 2-(2,3,4; 6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl-1,4-benzoquinones are dissolved in respectively in the chloroform, add Sodium Hydrosulphite (Na under the room temperature ₂S ₂O ₄) the aqueous solution, stirred 5-15 minute, reaction product is separated with column chromatography through extraction and is obtained 5-(2,3 respectively after removing inorganics, 4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl hydroquinone and 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3, the 5-dimethyl hydroquinone;

Wherein, 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl-1,4-benzoquinones or 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl-1,4-benzoquinones and Na ₂S ₂O ₄Mol ratio be 1: (3-6); Its reaction formula is as follows:

(5) 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-γ-vitamin-E and 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-ε-vitamin-E is synthetic:

With the synthetic 5-of institute (2 in the step (4); 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2; 3-dimethyl hydroquinone and 2-(2; 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3; the 5-dimethyl hydroquinone is dissolved in the chloroform respectively; add phytol and Zinc Chloride Anhydrous, lucifuge, under argon shield backflow 24-30 hour.Reaction finishes after-filtration, filtrate through salt wash, wash, drying and column chromatography obtain 5-(2 respectively after removing other by product and inorganics, 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-γ-vitamin-E (white crystals) and 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-ε-vitamin-E (faint yellow slurries);

Wherein, 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl hydroquinone or 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl hydroquinone and phytol and anhydrous ZnCl ₂Mol ratio be 1: (0 8-2): (3-6); Its reaction formula is as follows:

(6) 5-(β-D-pyranoglucose)-γ-vitamin-E (compound 1) and 8-(β-D-pyranoglucose)-ε-vitamin-E (compound 2) is synthetic:

With step (5) the synthetic 5-of institute (2; 3; 4; 6-four-0-ethanoyl-β-D-pyranoglucose)-γ-vitamin-E and 8-(2; 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-ε-vitamin-E adds in the methanol solution of sodium methylate under argon shield respectively; stirred 2-3 hour under the room temperature, add excessive acidic cation-exchange resin IR-120 ⁺Neutralization reaction liquid filters, and filtrate decompression concentrates through the column chromatography purification and obtains target compound (compound 1 and compound 2) respectively,

Wherein, the mol ratio of 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-γ-vitamin-E or 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-ε-vitamin-E and sodium methylate is (2-4): 1; Its reaction formula is as follows:

Compound 1

Compound 2

(7) 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2,2,7,8-tetramethyl-benzo dihydropyrane and 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2,2,5,7-tetramethyl-benzo dihydropyrane synthetic:

Will be by the synthetic 5-of institute (2 in the step (4); 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2; 3-dimethyl hydroquinone and 2-(2; 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3; the 5-dimethyl hydroquinone is dissolved in the chloroform respectively; add the pure and mild Zinc Chloride Anhydrous of 3-methyl-2-butene-1-then, lucifuge, under argon shield backflow 24-30 hour.Reaction finishes after-filtration, and filtrate is washed, washed, after drying and column chromatography remove other by product, obtains 5-(2 respectively through salt, 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2,2,7,8-tetramethyl-benzo dihydropyrane (white crystal) and 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2,2,5,7-tetramethyl-benzo dihydropyrane (faint yellow slurries);

Wherein, 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl hydroquinone or 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl hydroquinone and the pure and mild ZnCl of 3-methyl-2-butene-1- ₂Mol ratio be 1: (0.8-2): (3-6); Its reaction formula is as follows:

(8) 5-(β-D-pyranoglucose)-6-hydroxyl-2,2,7,8-tetramethyl-benzo dihydropyrane (compound 3) and 8-(β-D-pyranoglucose)-6-hydroxyl-2,2,5,7-tetramethyl-benzo dihydropyrane (compound 4) synthetic:

With step (7) the synthetic 5-of institute (2,3,4; 6-four-0-ethanoyl-β-D-pyranoglucose)-and 6-hydroxyl-2,2,7; 8-tetramethyl-benzo dihydropyrane and 8-(2,3,4; 6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2; 2,5,7-tetramethyl-benzo dihydropyrane adds in the methanol solution of sodium methylate under argon shield respectively; stirred 2-3 hour under the room temperature, add excessive acidic cation-exchange resin IR-120 again ⁺Neutralization reaction liquid, filter, filtrate decompression concentrates and obtains target compound (compound 3 and compound 4) respectively through the column chromatography purification is 5-(β-D-pyranoglucose)-6-hydroxyl-2,2,7,8-tetramethyl-benzo dihydropyrane (compound 3) and 8-(β-D-pyranoglucose)-6-hydroxyl-2,2,5,7-tetramethyl-benzo dihydropyrane (compound 4);

Wherein, 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2,2,7,8-tetramethyl-benzo dihydropyrane or 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2,2,5, the mol ratio of 7-tetramethyl-benzo dihydropyrane and sodium methylate is (2-4): 1; Reaction formula is as follows:

Compound 3

Compound 4

Said other compound of the present invention can adopt method preparation similar to the above, and used reagent is commercially available product in the starting raw material that relates in described preparation method and each the step reaction.

The present invention successfully introduces pyranoglucose by rational synthesis step on the phenyl ring of parent chroman of tocopherols compound or its analogue, keeping under chroman derivatives (tocopherols compound or its analogue) the anti-oxidant activity prerequisite, improving that it is water-soluble.For the Application Areas of widening vitamin-E or its analogue is laid a good foundation.

Embodiment

The invention will be further elaborated by the following examples, and its purpose only is better to understand content of the present invention and unrestricted protection scope of the present invention:

Embodiment 1

Synthesizing of compound 1 and compound 3:

(1) 1,4-is to methoxyl group-2,3-dimethyl benzene synthetic:

With 2, (1.38g 0.01mol) is dissolved in the 8mL dimethyl sulfoxide (DMSO) (DMSO) the 3-dimethyl hydroquinone, stir add down methyl iodide (3.2mL, 7.3g, 0.05mol) and KOH (4g, 0.07mol) solid, room temperature reaction 5 hours, thin plate chromatography (TLC) show that reaction finishes.Add water 20mL and stirred 5 minutes, use CH again ₂Cl ₂Extract repeatedly, the combined dichloromethane extraction liquid is successively used saturated Na ₂S ₂O ₃Saturated solution and saturated common salt water washing, anhydrous magnesium sulfate drying.Filter, organic phase decompression rotary evaporation removes and desolvates, and enriched material separates through a short column, with sherwood oil and CH ₂Cl ₂Mixed solvent (volume ratio is 2: 1) carry out wash-out, elutriant obtains white crystals 1 after solvent removed by evaporation at reduced pressure, 4-is to methoxyl group-2, the 3-dimethyl benzene;

(2) 1-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,5-dimethoxy-3,4-dimethyl benzene synthetic:

With 1,2,3,4, and 6-five-0-ethanoyl-β-D-pyranoglucose (985mg, 2.5mmol) and step (1) institute synthetic 1,4-is to methoxyl group-2, and (830mg, 5.0mmol 2eq) are dissolved in 12mLCH to the 3-dimethyl benzene ₂Cl ₂In, 25 ℃ condition stirred for several minute, treat that raw material dissolves fully after, (3.75mmol, 1.5eq), shading keeps 25 ℃ of system temperatures, slowly drips 1MSnCl under protection of inert gas to add catalyzer trifluoroacetic acid silver (AgOTfa) 831mg ₄CH ₂Cl ₂Solution 7.5ml (7.5mmol, 3eq).Stirring reaction, thin plate chromatography (TLC) shows that reaction finishes, and adds saturated NaHCO after 4 hours ₃Aqueous solution 40mL stirred 20 minutes, and suction filtration is removed inorganics, filtrate with dichloromethane extraction repeatedly, the combined dichloromethane extraction liquid is with saturated common salt solution washing, anhydrous magnesium sulfate drying.Filter; organic phase decompression rotary evaporation removes and desolvates; laboratory chromatography column commonly used separates on the enriched material, carries out wash-out with the mixed solvent (volume ratio is 2: 1) of sherwood oil and ethyl acetate, and elutriant is after solvent removed by evaporation at reduced pressure; obtain 1-(2; 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2; 5-dimethoxy-3, the 4-dimethyl benzene.Recrystallization gets white crystals 825mg with the mixed solvent of ether and sherwood oil, and productive rate 66.5% is stand-by.

The product test result is:

White crystal, mp89.5-91 ℃ (ether/sherwood oil); (developping agent is sherwood oil and ethyl acetate=1: 2 to Rf=0.43, v/v); [α] _D ²²=-20.8 (c=0.76, methylene dichloride);

¹H-NMR(CDCl ₃，200MHz)：6.71(s，1H，Ar-H)，5.52(t，1H，J＝9.1，9.9Hz，H _2’)，5.38(t，1H，J＝9.1Hz，H _3’)，5.24(t，1H，J＝9.1，9.7Hz，H _4’)，4.90(d，1H，J＝10Hz，H _1’)，4.24(dd，1H，J＝12.3，5.0Hz，H _6a’)，4.12(dd，1H，J＝12.3，2.3Hz，H _6b’)，3.90(ddd，1H，J＝2.3，5.0，9.7Hz，H _5’)，3.81(s，3H，OMe)，3.72(s，3H，OMe)，2.21，2.12，2.07，2.04，2.03，1.80(6s，18H，CH ₃).

¹³C-NMR (CDCl ₃, 50MHz): 170.7,170.4,169.6,169.3 (C=O, ethanoyl), 154.0,151.2 (C ₁, C ₄), 131.0,128.1,125.3 (C ₂, C ₅, C ₆), 106.6 (C ₃), 76.2,74.9,74.5,70.8,68.9 (C _{1 '}, C _{2 '}, C _{3 '}, C _{4 '}, C _{5 '}), 62.7 (C _{6 '}), 62.0,55.8 (OCH ₃), 20.8,20.7,20.7,20.6 (CH ₃, ethanoyl), 12.8,12.2 (CH ₃, Ar).

Ultimate analysis (C ₂₄H ₃₂O ₁₁): theoretical value: C, 58.06; H, 6.50; O, 35.45. actual value: C, 57.94; H, 6.62; O, 34.90.

(3) 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl-1,4-benzoquinones synthetic:

With step (2) the synthetic 1-of institute (2; 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2; 5-dimethoxy-3; (1120mg 2.26mmo1) is dissolved in the 4mL acetonitrile 4-dimethyl benzene, drips cerous ammonium nitrate (3717mg under the room temperature; 6.78mmol; aqueous solution 5mL 3eq) stirred 25 minutes, and TLC shows that reaction finishes.Reaction solution dichloromethane extraction, organic phase saturated common salt solution washing, anhydrous magnesium sulfate drying.Filter, the liquid residue underpressure distillation removes and desolvates, and gets 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl-1,4-benzoquinones 1028mg, productive rate 97.6%.

The product test result is as follows:

Yellow needle-like crystal, mp119-120 ℃ (methylene dichloride/sherwood oil); Rf=0.45 (developping agent is a sherwood oil: ethyl acetate=2: 1, v/v); [α] _D ²⁵=-1.2 (c=0.8, methylene dichloride); IR (KBr): 1760 (C=O, ethanoyl), 1650 (C=O, benzoquinones);

¹H-NMR(CDCl ₃，200?MHz)：6.80(d，1H，J＝0.8Hz，Ar)，5.34(t，1H，J＝9.2，9.4Hz，H _3’)，5.11(t，1H，J＝9.4，10.0Hz，H _4’)，4.97(t，1H，J＝9.2，9.7Hz，H _2’)，4.66(dd，1H，J＝9.7，0.8Hz，H _1’)，4.20(dd，1H，J＝4.7，12.4Hz，H _6a’)，4.10(dd，1H，J＝2.3，12.4Hz，H _6b’)，3.79(ddd，1H，H _5’)，2.06，2.02，1.99，1.99，1.98，1.87(6s，18H，CH ₃).

¹³C-NMR (CDCl ₃, 50MHz): 186.9,185.7 (C=O, benzoquinones), 170.6,170.1,169.7,169.5 (C=O, ethanoyl), 143.4,141.0,140.9 (C ₂, C ₅, C ₆), 133.4 (C ₃), 76.2,73.8,72.3,72.2,68.3 (C _{1 '}, C _{2 '}, C _{3 '}, C _{4 '}, C _{5 '}), 62.0 (C _{6 '}), 20.8,20.6,20.6,20.5 (CH ₃, ethanoyl), 12.4,12.2 (benzoquinones-CH ₃).

Ultimate analysis (C ₂₂H ₂₆O ₁₁): theoretical value: C, 56.65; O, 5.62; O, 37.73. actual value: C, 56.56; H, 5.97; O, 36.77.

(4) 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl hydroquinone synthetic:

With step (3) the synthetic 5-of institute (2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl-1, (932mg 2mmol) is dissolved in the 6mL chloroform 4-benzoquinones, adds Na under the room temperature ₂S ₂O ₄(2052mg, 12mmol, aqueous solution 7mL 6eq), vigorous stirring 10 minutes, TLC shows that reaction finishes.Isolate organic phase, water chloroform extraction 2 times merge organic phase, saturated common salt washing twice, anhydrous MgSO ₄Dry 3-4 hour, to filter, filtrate decompression is spin-dried for solvent, and (eluent is a methylene dichloride to residue: ethyl acetate=8: 1 through column chromatography; v/v) obtain product 5-(2,3,4; 6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl hydroquinone 820mg (1.752mmol), productive rate 87.6%.

The product test result is as follows:

White crystal, mp:192-193 ℃ (methylene dichloride/sherwood oil); Rf=0.21 (developping agent is a methylene dichloride: ethyl acetate=8: 1, v/v); [α] _D ²⁵=-37 (c=0.8, chloroforms);

¹H-NMR(CDCl ₃，200MHz)：6.49(s，1H，OH，Ar)，6.35(s，1H，Ar-H)，5.37-5.23(m，3H，H _2’，H _3’，H _4’)，4.87(s，1H，OH，Ar)，4.52(br?d，1H，J＝8.0Hz，H _1’)，4.32(dd，1H，J＝3.8Hz，12.4Hz，H _6a’)，4.16(d，1H，J＝12.4Hz，H _6b’)，3.89(m，1H，H _5’)，2.16，2.13，2.12，2.06，2.01，1.86(6s，18H，CH ₃).

¹³C-NMR (CDCl ₃, 50MHz): 170.8,170.5,169.5,169.0 (C=O, ethanoyl), 146.8,146.8 (C ₁, C ₄, Ar), 126.6,125.1,117.6 (C ₂, C ₅, C ₆, Ar), 111.7 (C ₃, Ar), 80.0,76.1,73.9,70.7,68.0 (C _{1 '}, C _{2 '}, C _{3 '}, C _{4 '}, C _{5 '}), 61.7 (C _{6 '}), 20.7,20.7,20.6,20.5 (CH ₃, ethanoyl), 12.2,12.1 (Ar-CH ₃).

Ultimate analysis (C ₂₂H ₂₈O ₁₁): theoretical value: C, 56.41; H, 6.02; O, 37.57 actual values: C, 56.15; H, 6.22; O, 37.26.

(5) 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-γ-vitamin-E is synthetic:

With step (4) the synthetic 5-of institute (2; 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2; 3-dimethyl hydroquinone (270mg; 0.577mmol) be dissolved in the 5mL chloroform, (0.556mmol is 0.96eq) with Zinc Chloride Anhydrous 453.7mg (3.336mmol to add phytol 0.2mL; 6eq); system's lucifuge refluxed 26 hours under argon shield, and TLC shows the basic end of reaction.Reaction mixture is filtered, and filtrate is earlier after NaHCO ₃Saturated solution, saturated common salt washing, anhydrous MgSO ₄Dry 3-4 hour.Filter, filtrate decompression is spin-dried for solvent, and (eluent is a sherwood oil to residue: ethyl acetate=3: 1 through column chromatography; v/v), promptly obtain product white crystals 5-(2,3; 4,6-four-0-ethanoyl-β-D-pyranoglucose)-γ-vitamin-E (formula 1) 272mg (0.365mmol), productive rate 65.6%.

The product test result is as follows:

White crystal, mp:144-146 ℃ (methylene dichloride/sherwood oil); Rf=0.20 (developping agent is a sherwood oil: ethyl acetate=3: 1, v/v); [α] _D ²²=-0.227 (c=0.88, methylene dichloride);

¹H-NMR (CDCl ₃, 200MHz): 6.93,6.90 (2s, 1H, Ar-OH), 5.58 (t, 1H, J=7.9,9.9Hz, H _{2 "}), 5.35-5.30 (m, 2H, H _{3 "}, H _{4 "}), 4.86 (d, 1H, J=9.9Hz, H _{1 "}), 4.33 (dd, 1H, J=2.9,12.4Hz, H _{6a "}), 4.15 (d, 1H, J=12.4Hz, H _{6b "}), 3.89 (m, 1H, H _{5 "}), 2.70 (t, 2H, J=6.5Hz, H _{4 a, b}), 2.14,2.14,2.08,2.06,2.01,1.82 (6s, 18H, CH ₃), 1.75 (2H is capped, H _{3a, b}), 1.60-1.0 (m, 24H, H _{1 '-12 '}, H _2a), 0.89-0.86 (m, 12H, Me _{13 ', 4 ' a, 8 ' a, 12 ' a}).

¹³C-NMR (CDCl ₃, 50MHz): 170.7,170.5,169.3,168.4 (C=O, ethanoyl), 146.8,144.9 (C ₆, C _8a), 127.6,124.9,115.6,114.9 (C ₅, C ₇, C ₈, C _4a), 76.2,76.2,74.2,70.3,67.8 (C _{1 "}, C _{2 "}, C _{3 "}, C _{4 "}, C _{5 "}), 74.4 (C ₂), 61.4 (C _{6 "}), 39.4,39.4,37.4,37.4,37.3,31.7,24.8,24.5,21.0,20.6,20.6 (methylene radical: C ₃, C ₄, C _{1 '}, C _{2 '}, C _{3 '}, C _{5 '}, C _{6 '}, C _{7 '}, C _{9 '}, C _{10 '}, C _{11 '}), 32.8,28.0,23.5,22.8,22.6,20.4,19.8,19.7 (C _{4 '}, C _{A '}, C _{12 '}, C _{13 '}, C _{4 ' a}, C _{8 ' a}, C _{12 ' a}, C _2a), 20.7,20.7,20.6,20.6 (CH ₃, ethanoyl), 12.2,11.9 (C _7qa, C _Ab).

Ultimate analysis (C ₄₂H ₆₆O ₁₁): theoretical value: C, 67.53; H, 8.91; O, 23.56. actual value: C, 67.56; H, 8.83; O, 22.67.

(6) synthetic (compound 1) of 5-(β-D-pyranoglucose)-γ-vitamin-E:

With step (5) the synthetic 5-of institute (2; 3; 4; 6-four-0-ethanoyl-β-D-pyranoglucose)-γ-vitamin-E (405 mg; 0.54mmol) under argon shield, add among methanol solution (0.1M) 5mL of sodium methylate; stirred 3 hours under the room temperature, add excessive a little acidic cation-exchange resin IR-120 ⁺Neutralization reaction liquid, stir after 5 minutes, filter, filtrate decompression concentrates, (proportioning of eluent is followed successively by residue: ethyl acetate: methylene dichloride=2: 1 with linear gradient elution method through column chromatography, 4: 1,8: 1, v/v is pure ethyl acetate at last) obtain three portion of product (chiral isomer), promptly (β-D-pyranoglucose)-γ-vitamin-E (2S) is (70.4mg) for 5-, 5-(β-D-pyranoglucose)-γ-vitamin-E (2S, 2R) (125.5mg), 5-(β-D-pyranoglucose)-γ-vitamin-E (2R) (100.6mg), overall yield 95%.

The solvability of compound 1 is: being slightly soluble in water, very easily being dissolved in acetone, methyl alcohol, pyridine, DMSO, is moderate solubility in chloroform.Its test result is as follows:

5-(β-D-pyranoglucose)-γ-vitamin-E (2S): light yellow solid, [α] _D ²²=+28.5 (c=1, acetone); Rf=0.50 (developping agent is a pure ethyl acetate);

¹H-NMR (acetone-d ₆, 500MHz): 7.76 (s, 1H, Ar-OH), 4.73 (d, 1H, J=9.5Hz, H _{1 "}), 4.72,4.47,4.26,3.13 (4br signals, 4H, sugar-OH), 3.90-3.83 (m, 2H, H _{6a "}, H _{6b "}), 3.77 (t, 1H, J=9.5,8.8Hz, H _{2 "}), 3.71 (t, 1H, J=8.8,9.2Hz, H _{4 "}), 3.60 (t, 1H, J _3,4=8.8Hz, H _{3 "}), 3.49 (br d, 1H, J=9.2Hz, H _{5 "}), 3.00 (m, 1H, H _4a), 2.64 (m, 1H, H _4b), 2.07,2.07 (2s, 6H, Me _7a, Me _Gb), 1.75 (m, 2H, H _{3a, b}), 1.59-1.13 (m, 21H, H _{1 '-12 '}), 1.22 (s, 3H, H _2a), 0.91-0.89 (m, 12H, H _{13 '}, H _{4 ' a}, H _{8 ' a}, H _{12 ' a}).

¹³C-NMR (acetone-d ₆, 125MHz): 147.2 (C ₆), 144.8 (C _8a), 125.1 (C ₈), 123.1 (C ₇), 119.0 (C ₅), 117.7 (C _4a), 81.3 (C _{5 "}), 78.8 (C _{3 "}), 78.3 (C _{1 "}), 74.5 (C ₂), 73.3 (C _{2 "}), 70.0 (C _{4 "}), 61.2 (C _{6 "}), 31.9,31.8 (C ₃), 20.7 (C ₄), 40.3,40.1,39.6,38.0,37.9,37.9,37.9,37.7,37.7,37.6,25.1,24.7,21.4,21.3,20.7 (C _{1 '}, C _{2 '}, C _{3 '}, C _{5 '}, C _{6 '}, C _{7 '}, C _{9 '}, C _{10 '}, C _{11 '}), 33.1,33.0,32.9,28.2,23.6,22.6,22.5,19.7,19.7,19.6,19.5 (C _{4 '}, C _{8 '}, C _{12 '}, C _{13 '}, C _{4 ' a}, C _{8 ' a}, C _{12 ' a}, C _2a), 11.8,11.6 (C _7a, C _8b).

MS(ESI+C)：m/z?1179.3[2M+Na] ⁺(100％)，578.3[M] ⁺(30％).

(ESI-C): m/z 1190.8[2M+C1] _-(40%), 613.2[M+Cl] _-(100%), 577.2[M-H] _-(20%) .5-(β-D-pyranoglucose)-γ-vitamin-E (2R): light yellow solid, [α] _D ²²=+42.4 (c=1, acetone); Rf=0.43 (developping agent is a pure ethyl acetate);

¹H-NMR (acetone-d ₆, 500MHz): 7.79 (s, 1H, Ar-OH), 4.73 (d, 1H, J=9.5Hz, H _{1 "}), 4.62,4.47,4.19,3.01 (4s, 4H, sugar-OH), 3.89-3.83 (m, 2H, H _{6a "}, H _{6b "}), 3.75 (t, 1H, J=9.5,8.8Hz, H _{2 "}), 3.70 (t, 1H, J=8.8,9.8Hz, H _{4 "}), 3.58 (t, 1H, J=8.8Hz, H _{3 "}), 3.49 (dt, 1H, J=9.5Hz, H _{5 "}), 2.96 (m, 1H, H _4a), 2.68 (dt, 1H, J=6.3,6.6Hz, J _Gem=16.4H _4b), 2.07,2.07 (s, 6H, Me _7a, Me _8b), 1.74 (t, 2H, J=6.6Hz, H _{3a, b}), 1.62-1.11 (m, 21H, H _{1 '-12 '}), 1.22 (s, 3H, H _2a), 0.90-0.88 (m, 12H, H _{13 '}, H _{4 ' a}, H _{8 ' a}, H _{12 ' a}).

¹³C-NMR (acetone-d ₆, 50MHz): 148.2 (C ₆), 145.9 (C _8a), 126.2 (C ₈), 124.2 (C ₇), 120.2 (C ₅), 118.8 (C _4a), 82.5 (C _{5 "}), 80.0 (C _{3 "}), 79.5 (C _{1 "}), 75.6 (C ₂), 74.5 (C _{2 "}), 71.3 (C _{4 "}), 62.4 (C _{6 "}), 33.1 (C ₃), 21.9 (C ₄), 41.4,40.7,39.1,38.8,38.6,26.2,26.2,25.8,22.4 (C _{1 '}, C _{2 '}, C _{3 '}, C _{5 '}, C _{6 '}, C _{7 '}, C _{9 '}, C _{10 '}, C _{11 '}), 33.0,32.9,28.2,23.6,22.6,22.5,19.7,19.6 (C _{4 '}, C _{8 '}, C _{12 '}, C _{13 '}, C _{4 ' a}, C _{8 ' a}, C _{12 ' a}, C _2a), 11.8,11.6 (Me _7a, Me _8b).

MS(ESI+C)：m/z?1179.3[2M+Na] ⁺(65％)，578.3[M] ⁺(100％).

(ESI-C)：m/z?1190.9[2M+Cl] ^-(65％)，613.2[M+Cl] ^-(100％)，577.3[M-H] ^-(65％).

(7) 5-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2,2,7,8-tetramethyl-benzo dihydropyrane synthetic:

With step (4) the synthetic 5-of institute (2; 3; 4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,3-dimethyl hydroquinone (560mg; 1.2mmol) be dissolved in the 5mL chloroform; adding 3-methyl-2-butene-1-alcohol 0.123mL (1.19mmol) and Zinc Chloride Anhydrous 979mg (7.2mmol, 6eq), system's lucifuge; refluxed 26 hours under argon shield, TLC shows the basic end of reaction.Reaction mixture is filtered, and filtrate is earlier after NaHCO ₃Saturated solution, saturated common salt washing, anhydrous MgSO ₄Dry 3-4 hour.Filter; filtrate decompression is spin-dried for solvent, residue through column chromatography (eluent is a sherwood oil: ethyl acetate=2: 1, v/v); promptly obtain product 5-(2; 3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2; 2; 7,8-tetramethyl-benzo dihydropyrane (white crystals) 384mg (0.716mmol), productive rate 60%.

The test result of product is:

White crystals, mp:205-206.5 ℃ (methylene dichloride/sherwood oil); Rf=0.23 (developping agent is a sherwood oil: ethyl acetate=2: 1, v/v); [α] _D ²²=-4.4 (c=0.9, methylene dichloride).

¹H-NMR (CDCl ₃, 200MHz): 6.93 (s, 1H, Ar-OH), 5.58 (t, 1H, J=9.3,10.0Hz, H _{2 '}), 5.35-5.31 (m, 2H, H _{3 '}, H _{4 '}), 4.86 (d, 1H, J=10.0Hz, H _{1 '}), 4.33 (dd, 1H, J=3.14Hz, 12.5Hz, H _{6a '}), 4.14 (dd, 1H, J=2.0,12.5Hz, H _{6b '}), 3.86 (m, 1H, H _{5 '}), 2.72 (t, 2H, J=6.7Hz, 2H ₄), 2.14,2.14 2.07,2.06,2.01,1.81 (6s, 18H, 4 OAc, Me _7a, Me _8b), 1.75 (2H is capped, 2H ₃), 1.29,1.23 (2s, 6H, Me _2a, Me _2b).

¹³C-NMR (CDCl ₃, 50.32MHz): 170.7,170.5,169.3,168.4 (C=O, ethanoyl), 146.9,145.0 (C ₆, C _8a, Ar), 127.6,124.9,115.4,114.9 (C ₅, C ₇, C ₈, C _4a, Ar), 76.2,76.2,74.2,70.3,67.7 (C _{1 '}, C _{2 '}, C _{3 '}, C _{4 '}, C _{5 '}), 72.4 (C ₂), 61.4 (C _{6 '}), 33.1,20.8 (C ₃, C ₄), 26.9,26.3 (C _2a, C _2b), 20.7,20.7,20.6,20.4 (CH ₃, ethanoyl), 12.2,11.9 (Me _7a, Me _8b).

Ultimate analysis (C ₂₇H ₃₆O ₁₁): theoretical value: C, 60.44; H, 6.76; O, 32.80. actual value: C, 59.98; H, 6.74; O, 33.75.

(8) 5-(β-D-pyranoglucose)-6-hydroxyl-2,2,7, synthetic (compound 3) of 8-tetramethyl-benzo dihydropyrane:

With step (7) the synthetic 5-of institute (2; 3; 4; 6-four-0-ethanoyl-β-D-pyranoglucose)-and 6-hydroxyl-2,2,7; 8-tetramethyl-benzo dihydropyrane (268mg; 0.5mmol) under argon shield, add among methanol solution (0.1M) 4mL of sodium methylate, stirred 3 hours under the room temperature, add excessive a little acidic cation-exchange resin IR-120 ⁺Neutralization reaction liquid stirred after 5 minutes, filtered, and filtrate decompression concentrates, and residue obtains 168.4mg white solid product (being compound 3), productive rate 91.5% through column chromatography (eluent is a pure ethyl acetate).

The solvability of compound 3 is, and is water-soluble, very easily is dissolved in acetone, methyl alcohol, pyridine, DMSO, is slightly soluble in chloroform.Its structured testing result is:

White solid, mp135-137 ℃ (ethylacetate/ether); Rf=0.23 (developping agent is a pure ethyl acetate); [α] _D ²²=+48.2 (c=0.7, acetone);

¹H-NMR (acetone-d ₆, 500MHz): 7.75 (s, 1H, Ar-OH), 4.74 (d, 1H, J=9.5Hz, H _{1 '}), 4.43,4.39,4.09 (3br signals, 3H, sugar-OH), 3.90-3.84 (m, 2H, H _{6a '}, H _{6b '}), 3.76 (t, 1H, J=9.5,9.1Hz, H _{2 '}), 3.69 (t, 1H, J=9.1,9.5Hz, H _{4 '}), 3.58 (t, 1H, J=9.1,8.8Hz, H _{3 '}), 3.50 (dt, 1H, J=9.5,3.1Hz, H _{5 '}), 2.98 (m, 2H are capped, sugar-OH, H _4a), 2.68 (dt, 1H, J _Gem=16.4Hz, J=6.6Hz, H _4b), 2.07,2.05 (2s, 6H, Me _7a, Me _8b), 1.74 (m, 2H, H _{3a, b}), 1.28,1.25 (2s, 6H, Me _2a, Me _2b).

¹³C-NMR (acetone-d ₆, 125MHz): 147.3 (C ₆), 145.0 (C _8a), 125.1 (C ₈), 123.1 (C ₇), 119.0 (C ₅), 117.5 (C _4a), 81.3 (C _{5 '}), 79.0 (C _{3 '}), 78.4 (C _{1 '}), 73.4 (C _{2 '}), 72.5 (C ₂), 70.2 (C _{4 '}), 61.3 (C _{6 '}), 33.3 (C ₃), 26.8,26.2 (C _2a, C _2b), ^*21.1 (C ₄), 11.7,11.5 (C _7a, C _8b).

MS(ESI+C)：m/z?759.0[2M+Na] ⁺(100％)，391.1[M+Na] ⁺(15％)，369.0[M+H] ⁺(10％).

(ESI-C)：m/z?770.7[2M+Cl] ^-(10％)，402.8[M+Cl] ^-(100％)，367.0[M-H] ^-(85％).

Embodiment 2

Synthesizing of compound 2 and compound 4:

(1) 1,4-is to methoxyl group-2,6-dimethyl benzene synthetic:

(34g 0.50mol) is dissolved under ice bath in the 100mL water, drops into the trash ice of 200g, stirs the two sodium sulfate (Na that lay particular stress on that drip 100mL down with Sodium Nitrite ₂S ₂O ₅) the aqueous solution (35%, w/v), add the 20mL Glacial acetic acid then.Add 25mL strong aqua (spgr0.8) after 3 minutes.(12.6g, aqueous solution 0.079mol) continue to stir 1 hour after-filtration, and the purple filtrate of gained is poured the saturated solution of the KCl in the 800mL stirring into to react the potassium permanganate that slowly drips 400mL after 30 minutes.Stir 1 hour after-filtration and promptly obtain Fermi's salt (Fremy ' s salt).Freshly prepared Fermi's salt is soluble in water under 0 ℃, stir down and slowly drip 2,6-xylenol (4.5g, methanol solution 400mL 0.037mol).Reaction afterreaction product dichloromethane extraction 3 times in 6-8 hour under the room temperature, the extraction liquid washing is again with obtaining yellow crystal 2 behind the anhydrous magnesium sulfate drying, 6-phlorone 4.2g, productive rate 83%.With obtain 2, the 6-phlorone is dissolved in the 10mL chloroform, adds Na ₂S ₂O ₄(21.5g, aqueous solution 12mL 4eq), under the room temperature vigorous stirring 10-20 minute, reaction mixture is removed chloroform through underpressure distillation, adds extracted with diethyl ether repeatedly, and combined ether layer obtains white solid 2 behind washing, anhydrous magnesium sulfate drying, 6-dimethyl hydroquinone 4.0g, productive rate 93.8%.

All the other operations are identical with embodiment 1 corresponding part step (1), obtain light yellow liquid 1, and 4-is to methoxyl group-2, and 6-dimethyl benzene, productive rate are 73.9%.

(2) 1-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,4-dimethyl-3,6-dimethoxy benzene synthetic:

Operation is identical with embodiment 1 corresponding part step (2), obtains 1-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-2,4-dimethyl-3, and 6-dimethoxy benzene, productive rate are 73.9%.

The product test result is as follows:

White foam, [α] _D ²²=-10.1 (c=0.86, methylene dichloride); (developping agent is sherwood oil and ethyl acetate=2: 1 to Rf=0.40, v/v);

¹H-NMR(DMSO-d ₆，300MHz，90℃)：6.69(s，1H，Ar-H)，5.54(t，1H，J＝9.3Hz，H _2’)，5.30(t，1H，J＝9.5，9.3Hz，H _3’)，5.10(d，1H，J＝9.3H _1’)，5.05(t，1H，J＝9.5，10.0Hz，H _4’)，4.16(dd，1H，J＝12.4，3.4Hz，H _6a’)，4.11(dd，1H，J＝12.4，4.1Hz，H _6b’)，4.00(m，1H，H _5’)，3.76(s，3H，OMe)，3.58(s，3H，OMe)，2.33，2.22，2.03，2.01，1.95，1.69(6s，18H，CH ₃).

¹³C-NMR (DMSO-d ₆, 75MHz, 90 ℃): 170.1,169.7,169.5,168.7 (C=O, ethanoyl), 154.6,151.3 (C ₁, C ₄), 131.8,131.7,121.7 (C ₂, C ₃, C ₅), 112.9 (C ₆), 75.4,74.7,73.6,70.6,69.2 (C _{1 '}, C _{2 '}, C _{3 '}, C _{4 '}, C _{5 '}), 62.5 (C _{6 '}), 59.8,56.9 (OCH ₃), 20.6,20.6,20.5,20.2 (CH ₃, ethanoyl), 16.4,12.5 (CH ₃, Ar) ultimate analysis (C ₂₄H ₃₂O ₁₁): theoretical value: C, 58.06; H, 6.50; O, 35.45. actual value: C, 57.76; H, 6.46; O, 35.95.

(3) 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl-1,4-benzoquinones synthetic:

Operation is identical with embodiment 1 corresponding part step (3), obtains 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl-1, and 4-benzoquinones, productive rate are 93.2%.

The product test result is as follows:

Yellow needle crystal, mp149-150.5 ℃ (methylene dichloride/sherwood oil); Rf=0.43, (developping agent is sherwood oil and ethyl acetate=1: 2, v/v); [α] _D ²²=-63 (c=0.7, methylene dichloride); IR (KBr): 1750 (C=O, ethanoyl), 1650 (C=O, benzoquinones).

¹H-NMR (500 MHz, CDCl ₃): 6.56 (d, 1H, J=1.4Hz, Ar-H), 5.43 (t, 1H, J=9.1,9.9Hz, H _{2 '}), 5.31 (t, 1H, J=9.1,9.7Hz, H _{3 '}), 5.20 (t, 1H, J=9.7Hz, H _{4 '}), 4.96 (d, 1H, J=9.9Hz, H _{1 '}), 4.20 (dd, 1H, J=2.6,12.5Hz, H _{6a '}), 4.17 (dd, 1H, J=4.0,12.5Hz, H _{6b '}), 3.76 (dq, 1H, H _{5 '}), 2.27,2.08,2.06,2.01,1.87 (5s, 15H, ethanoyl and 3 methyl), 2.04 (d, 3H, J=1.5Hz, 5 methyl).

¹³C-NMR (CDCl ₃, 50MHz): 187.7,185.3 (C=O, benzoquinones), 170.6,170.1,169.6,169.5 (C=O, ethanoyl), 145.9,145.8,136.8 (C ₂, C ₃, C ₅), 133.0 (C ₆), 76.3,74.2,71.9,70.2,68.3 (C _{1 '}, C _{2 '}, C _{3 '}, C _{4 '}, C _{5 '}), 61.9 (C _{6 '}), 20.7,20.6,20.6,20.4 (CH ₃, ethanoyl), 16.0,12.7 (CH ₃, benzoquinones)

Ultimate analysis (C ₂₂H ₂₆O ₁₁): theoretical value: C, 56.65; H, 5.62; O, 37.73. actual value: C, 56.57; H, 5.61; O, 37.50.

(4) 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl hydroquinone synthetic:

Operation is identical with embodiment 1 corresponding part step (4), obtains 2-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-3,5-dimethyl hydroquinone, productive rate 95%.

The product test result is as follows:

White crystal l, mp:198.5-200 ℃ (methylene dichloride/sherwood oil); Rf=0.17 (developping agent is a methylene dichloride: ethyl acetate=8: 1, v/v); [α] _D ²⁵=-23.9 (c=0.8, methylene dichloride).

¹H-NMR (CDCl ₃, 500MHz): 6.95 (s, 1H, OH), 6.58 (s, 1H, H ₆), 5.50 (t, 1H, J=9.5Hz, H _{2 '}), 5.37-5.30 (2 overlapping three peaks, 2H, H _{3 '}, H _{4 '}), 4.91 (d, 1H, J=9.9Hz, H _{1 '}), 4.32 (dd, 1H, J=2.3Hz, 12.5Hz, H _{6a '}), 4.25 (s, 1H, OH), 4.15 (dd, 1H, J=12.5,1.4Hz, H _{6b '}), 3.88 (m, 1H, H _{5 '}), 2.21,2.17,2.12,2.06,2.01,1.81 (6s, 18H, CH ₃) ¹H-NMR (CDCl ₃, 200MHz): 6.96 (s, 1H, OH), 6.58 (s, 1H, H ₆), 5.51 (m, 1H, H _{2 '}), 5.41-5.27 (m, 2H, H _{3 '}, H _{4 '}), 4.92 (d, 1H, J=9.8Hz, H _{1 '}), 4.33 (dd, 1H, J=3.0Hz, 12.5Hz, H _{6a '}), 4.2 (be capped, 1H, OH), 4.16 (dd, J=12.5,2.2Hz, H _{6b '}), 3.89 (m, 1H, H _{5 '}), 2.22,2.18,2.13,2.07,2.02,1.82 (6s, 18H, CH ₃);

¹³C-NMR (CDCl ₃, 50MHz): 170.7,170.4,169.4,168.6 (C=O, ethanoyl), 149.4,145.5 (C ₁, C ₄), 125.3,125.3,122.3 (C ₂, C ₃, C ₅, Ar), 117.6 (C ₆), 77.0,76.1,73.9,70.4,67.8 (C _{1 '}, C _{2 '}, C _{3 '}, C _{4 '}, C _{5 '}), 61.4 (C _{6 '}), 20.7,20.7,20.6,20.3 (CH ₃, ethanoyl), 16.3,12.3 (Ar-CH ₃).

Ultimate analysis (C ₂₂H ₂₈O ₁₁): theoretical value: C, 56.41; H, 6.02; O, 37.57. actual value: C, 56.03; H, 6.21; O, 37.51.

(5) 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-ε-vitamin-E is synthetic:

Operation is identical with embodiment 1 corresponding part step (5), obtains 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-ε-vitamin-E, productive rate 62.7%.

The product test data is as follows:

The red-brown syrup, (developping agent is sherwood oil and ethyl acetate=3: 1 to Rf=0.26, v/v); [α] _D ²⁵=+4.66 (c=0.88, methylene dichloride).

¹H-NMR(DMSO-d ₆，120℃，500MHz)：7.26(s，1H，Ar-OH，at?90?C)，5.64(br?signal，1H，H _2”)，5.234，5.227(2t，1H，J＝9.5，9.1Hz，H _3”)，5.11(br?signal，1H，H _1”)，5.10-5.04(m，1H，H _4”)，4.16(dd，1H，J＝3.2，12Hz，H _6”a)，4.11(dd，1H，J＝4.5，12Hz，H _6”b)，3.86(m，1H，H _5”)，2.57(m，2H，H _4a，H _4b)，2.27，2.08，2.02，2.00，1.94(5s，15H，2-ArCH ₃，3-OAc)，1.74(m，2H，H _3a，H _3b)，1.71(s，3H，C _2”-OAc)，1.61-1.12(m，24H，H _1’-12’，Me _2a)，0.93-0.87(m，12H，Me _{13’，4’a，8’a，12’a}).

¹³C-NMR (DMSO-d ₆, 120 ℃, 125MHz): 170.4,170.15,170.1,169.9,169.8,169.1 (C=O, ethanoyl), 146.5,125.3,125.3,125.2,125.1,120.4,120.2,118.5,118.4 (C ₆, C _8a, C ₅, C ₇, C ₈, C _4a), 76.3,76.0,71.6,70.2,70.1 (C _{1 "}, C _{2 "}, C _{3 "}, C _{4 "}, C _{5 "}), 75.7,75.6 (C ₂), 63.5,63.4 (C _{6 "}), 41.5,39.8,38.2,37.8,37.7,37.6,31.9,24.9,24.7,21.5,21.1 (methylene radical: C ₃, C ₄, C _{1 '}, C _{2 '}, C _{3 '}, C _{5 '}, C _{6 '}, C _{7 '}, C _{9 '}, C _{10 '}, C _{11 '}), 33.1,28.2,24.0,23.7,23.1,23.1,21.0,21.0,20.7,20.4,20.3 (C _{4 '}, C _{8 '}, C _{12 '}, C _{13 '}, C _{4 ' a}, C _{8 ' a}, C _{12 ' a}, C _2a), 20.4,20.3,20.3,20.3 (CH ₃, ethanoyl), 13.3,12.6 (C _7a, C _Ab).

MS (ESI+C): m/z:1515.6[2M+Na] ⁺, 55%, 769.4[M+Na] ⁺, 100%, 764.1[M+NH ₄] ⁺, 40%, 747.1[M+H] ⁺, 45%; HRMS (FAB, nitrobenzyl alcohol) theoretical value C ₄₂H ₆₇O ₁₁[M+H] ⁺: 747.4683. actual value: 747.46790.

(6) synthetic (compound 2) of 8-(β-D-pyranoglucose)-ε-vitamin-E:

Operation is identical with embodiment 1 corresponding part step (6), obtains 8-(β-D-pyranoglucose)-ε-vitamin-E (compound 2), productive rate 89%.

Compound 2 solvabilities are: being slightly soluble in water, very easily being dissolved in acetone, methyl alcohol, pyridine, DMSO, is moderate solubility in chloroform.

Compound 2 test results are as follows:

The red-brown solid, Rf=0.60 (developping agent is an ethyl acetate); [α] _D ²⁵=+18.8 (c=0.74, acetone).

Because compound 2 is for mixture that a plurality of chiral centres are arranged with because the steric hindrance relation makes glycosidic link (C-C key) not rotate freely, even cause under hot conditions [ ¹H-NMR (DMSO-d ₆, 90 ℃, 500MHz), ¹³C-NMR (DMSO-d ₆, 90 ℃, 125MHz)] can not obtain nuclear magnetic resonance spectrum clearly.

MS(ESI+C)：m/z：1179.4[2M+Na] ⁺(100％)，601.4[M+Na] ⁺(45％).

(ESI-C)：m/z：1191.2[2M+Cl] ^-(60％)，623.1[M+HCOO] ^-(100％)，577.3[M-H] ^-(45％).

(7) 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2,2,5,7-tetramethyl-benzo dihydropyrane synthetic:

Operation is identical with embodiment 1 corresponding part step (7), obtains 8-(2,3,4,6-four-0-ethanoyl-β-D-pyranoglucose)-6-hydroxyl-2,2,5,7-tetramethyl-benzo dihydropyrane, and productive rate is 48.2%.

The product test result is as follows:

White foam, (developping agent is sherwood oil and ethyl acetate=2: 1 to Rf=0.21, v/v); [α] _D ²⁵=-1.1 (c=0.8, methylene dichloride);

¹H-NMR (DMSO-d ₆, 120 ℃, 500MHz): 7.00 (s, 1H, Ar-OH), 5.65 (br triplet, 1H, H _{2 '}), 5.24 (t, 1H, J=9.1,9.5Hz, H _{3 '}), 5.11 (br doublet, 1H, H _{1 '}), 5.07 (t, 1H, J=9.5,9.8Hz, H _{4 '}), 4.14 (d, 2H, J=3.5Hz, H _{6a '}, H _{6b '}), 3.91 (dt, 1H, J=9.8,3.8Hz, H _{5 '}), 2.58 (t, 2H, J=6.9Hz, H _4ab), 2.27,2.08 (2s, 6H, Me _5a, Me _7a), 2.03,2.00,1.95,1.71 (4s, 12H, 4 ethanoyl), 1.77 (t, 2H, J=6.9,6.6Hz, H _3ab), 1.33,1.29 (2s, 6H, Me _2a, Me _2b).

¹³C-NMR (DMSO-d ₆, 120 ℃, 125MHz)): 170.5,170.2,169.9,169.2 (C=O, ethanoyl), 146.8,146.5 (C ₆, C _8a), ^*125.3,125.1,120.4,118.3 (C ₅, C ₇, C ₈, C _4a), ^*76.0,76.0,74.5,71.7,70.0 (C _{1 '}, C _{2 '}, C _{3 '}, C _{4 '}, C _{5 '}), ^*73.5 (C ₂), 63.4 (C _{6 '}), 33.6,21.4 (C ₃, C ₄), ^*27.6,27.0 (C _2a, C _2b), 21.4,21.0,21.0,20.8 (CH ₃, ethanoyl), 13.3,12.6 (Me _7a, Me _8b).

Ultimate analysis (C ₂₇H ₃₆O ₁₁): theoretical value: C, 60.44; H, 6.76; O, 32.80. actual value: C, 60.92; H, 7.05; O, 31.23

(8) 8-(β-D-pyranoglucose)-6-hydroxyl-2,2,5,7-tetramethyl-benzo dihydropyrane (compound 4) synthetic:

Operation is identical with embodiment 1 corresponding part step (8), obtains 8-(β-D-pyranoglucose)-6-hydroxyl-2,2,5,7-tetramethyl-benzo dihydropyrane (compound 4), and productive rate is 93%.

Compound 4 solvabilities are, and are water-soluble, very easily are dissolved in acetone, methyl alcohol, pyridine, DMSO, are slightly soluble in chloroform.Its test result is as follows:

White solid, Rf=0.19 (developping agent is an ethyl acetate); [α] _D ²⁵=+18.3 (c=0.6, methyl alcohol);

¹H-NMR(DMSO-d ₆+D ₂O，90℃，500MHz)：4.68(br?signal，1H，H _1’)，3.86(br?signal，1H，H _2’)，3.71(dd，1H，J＝2.3，11.7Hz，H _6’a)，3.50(dd，1H，J＝5.1，11.7Hz，H _6’b)，3.30-3.20(m，3H，H _3’，H _4’，H _5’)，2.56(t，2H，J＝6.6，6.3Hz，H _4a，b)，2.22，2.06(2s，6H，Me _5a，Me _7a)，1.74(t，2H，J＝6.6，6.0Hz，H _3sa，b)，1.25，1.21(2s，6H，Me _2a，Me _2b).

¹³C-NMR(DMSO-d ₆+D ₂O，90℃，125MHz)：147.0，146.4(C ₆，C _8a)，124.9，123.9，123.8，118.2(C _4a，C ₅，C ₇，C ₈)，81.6，80.0，72.9，71.8，71.8(C _1’，C _2’，C _3’，C _4’，C _5’)，73.2(C ₂)，62.9(C _6’)，33.6(C ₃)，27.7，26.7(C _2a，C _2b)，21.5(C ₄)，13.8，12.6(C _5a，C _7a).

MS(ESI+C)m/z＝759.0[2M+Na] ⁺(100％)，391.1[M+Na] ⁺(27％)。

Claims

1, a kind of benzo-dihydropyran glycoside derivatives, it has following structural formula:

In the formula: R ₁, R ₃Be selected from H respectively, CH ₃With

In a kind of; R ₂Be C ₁-C ₁₆Alkyl; R ₄Be H or CH ₃

Wherein: R ₁And R ₃In at least one is But R ₁And R ₃Be not simultaneously

2, derivative as claimed in claim 1 is characterized in that, wherein R ₂Be C ₁～C ₁₆Chain-like alkyl.

3, derivative as claimed in claim 2 is characterized in that, wherein R ₂Be CH ₃Or

4, derivative as claimed in claim 3 is characterized in that, described derivative is compound 1, compound 2, compound 3 or compound 4.