CN104262422B - A kind of chemosynthesis 4-(3,4-dihydroxybenzoyl oxygen methyl) method of-phenyl-O-β-D-pyranglucoside - Google Patents
A kind of chemosynthesis 4-(3,4-dihydroxybenzoyl oxygen methyl) method of-phenyl-O-β-D-pyranglucoside Download PDFInfo
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Abstract
<b /><b /><b /><b /><b /><b /><b /><b /><b />the invention discloses a kind of chemosynthesis 4-(3,4-dihydroxybenzoyl oxygen methyl)-phenyl-<i>o</i>the method of-β-D-pyranglucoside, the steps include: 2,3,4,6-tetra--<i>o</i>-acetyl group-α-D-bromo Glucopyranose. with to hydroxy-benzyl alcohol in dry dipolar aprotic solvent, under the catalysis of Anhydrous potassium carbonate and cesium chloride accelerator prepare 4-hyd roxymethyl phenyl-<i>o</i>-β-D-2,3,4,6-four-<i>o</i>-acetyl group pyranglucoside, be then obtained by reacting in dry methylene chloride and acid binding agent with 3,4-diacetoxy Benzenecarbonyl chloride .s 4-(3,4-diacetoxy benzoyloxymethy)-phenyl-<i>o</i>-β-D-2,3,4,6-four-<i>o</i>-acetyl group pyranglucoside, then slough under the catalysis of stannum type oxide in absolute methanol sugar ring and phenyl ring on protection base obtain 4-(3,4-dihydroxybenzoyl oxygen methyl)-phenyl-<i>o</i>-β-D-pyranglucoside.The inventive method raw material is cheap and easy to get, and reactions steps is brief, it is not necessary to column chromatography for separation, and three waste discharge is few.
Description
Technical field
The invention belongs to field of fine chemical, be specifically related to a kind of chemosynthesis 4-(3,4-dihydroxybenzoyl oxygen methyl) method of-phenyl-O-β-D-pyranglucoside.
Background technology
4-(3; 4-dihydroxybenzoyl oxygen methyl)-phenyl-O-β-D-pyranglucoside is a kind of Polyphenols glucoside of separation and Extraction from Chinese herbal medicine Adeps Bovis seu Bubali; there is antioxidation and scavenging free radicals function, it is possible to protection hepatocyte and Skin Cell are from oxidative damage, thus can serve as cosmetics and food additive [Chia-HuaLiang; Leong-PengChan; Hisou-YuDing, etal., J.Agri.FoodandChem.; 2012,7690-7696].But, 4-(3,4-dihydroxybenzoyl oxygen methyl)-phenyl-O-β-D-pyranglucoside content very low (only 0.083%) [NobujiNakatani in Adeps Bovis seu Bubali, HiroeKikuzaki, Agri.Biol.Chem., 1987,51 (10), 2727-2732], 4-(3,4-dihydroxybenzoyl oxygen methyl is extracted from Adeps Bovis seu Bubali)-phenyl-O-β-D-pyranglucoside is very uneconomical, and destruction ecological resources, therefore 4-(3,4-dihydroxybenzoyl oxygen methyl is studied) synthesis of-phenyl-O-β-D-pyranglucoside is significant.
Summary of the invention
In view of separation and Extraction 4-(3 from Adeps Bovis seu Bubali, 4-dihydroxybenzoyl oxygen methyl) there is cost height in-phenyl-O-β-D-pyranglucoside, destroy the drawbacks such as ecological resources, the present inventor develops one on the basis of the big quantity research of early stage can chemosynthesis 4-(3,4-dihydroxybenzoyl oxygen methyl in a large number) method of-phenyl-O-β-D-pyranglucoside.
It is an object of the invention to provide a kind of easy to operate, cost is low, can scale synthesis 4-(3,4-dihydroxybenzoyl oxygen methyl) method of-phenyl-O-β-D-pyranglucoside.
Chemosynthesis 4-(3,4-dihydroxybenzoyl oxygen methyl of the present invention) method of-phenyl-O-β-D-pyranglucoside, its step is as follows:
1) by 2,3,4; 6-tetra--O-acetyl group-α-D-bromo Glucopyranose. with to hydroxy-benzyl alcohol in dry dipolar aprotic solvent, under the catalysis of Anhydrous potassium carbonate and cesium chloride accelerator prepare 4-hyd roxymethyl phenyl-O-β-D-2,3; 4,6-tetra--O-acetyl group pyranglucoside；
2) 4-hyd roxymethyl phenyl-O-β-D-2 step 1) obtained; 3; 4; 6-tetra--O-acetyl group pyranglucoside and 3; 4-diacetoxy Benzenecarbonyl chloride. is obtained by reacting 4-(3,4-diacetoxy benzoyloxymethy in dry chlorinated hydrocarbon organic solvent with acid binding agent)-phenyl O-β-D-2,3; 4,6-tetra--O-acetyl group pyranglucoside；
3) by step 2) 4-(3 that obtains; 4-diacetoxy benzoyloxymethy)-phenyl O-β-D-2; 3; 4; the Acetyl Protecting Groups that 6-tetra--O-acetyl group pyranglucoside is sloughed on sugar ring and phenyl ring in absolute alcohol kind solvent under the catalysis of stannum type oxide obtains target product 4-(3,4-dihydroxybenzoyl oxygen methyl)-phenyl-O-β-D-pyranglucoside.
Chemosynthesis 4-(3 of the present invention, 4-dihydroxybenzoyl oxygen methyl) reaction equation of-phenyl-O-β-D-pyranglucoside is as follows, wherein structural formula 1 is 4-(3, 4-dihydroxybenzoyl oxygen methyl)-phenyl-O-β-D-pyranglucoside, structural formula 2 is 2, 3, 4, 6-tetra--O-acetyl group-α-D-bromo Glucopyranose., structural formula 3 is p-Hydroxybenzylalcohol, structural formula 4 is 4-hyd roxymethyl phenyl-O-β-D-2, 3, 4, 6-tetra--O-acetyl group pyranglucoside, structural formula 5 is 3, 4-diacetoxy Benzenecarbonyl chloride., structural formula 6 is 4-(3, 4-diacetoxy benzoyloxymethy)-phenyl O-β-D-2, 3, 4, 6-tetra--O-acetyl group pyranglucoside.
Benefit of the invention is that: reactions steps is few, reaction raw materials is cheap and easy to get, and each step product is without column chromatography for separation, and cost is low, and three waste discharge is few, is suitable for industrialized production.
Detailed description of the invention
Embodiment 1
By 2; 3; 4; 6-tetra--O-acetyl group-α-D-bromo Glucopyranose. (50mmol, 20.5g) is dissolved in 50 milliliters of dry DMF, adds p-Hydroxybenzylalcohol (55mmol; 6.85g) and Anhydrous potassium carbonate (60mmol; 8.3g), and addition catalytic amount (2.5mmol, 0; cesium chloride 42g); room temperature reaction 2 hours, is poured in frozen water by reactant mixture, precipitates out white solid; collect by filtration white solid; gained white solid dehydrated alcohol recrystallization obtains white crystal 16.2g, yield 71%, fusing point 108.9-109.7 DEG C.
1HNMR(400MHz,CDCl3)d2.04,2.05,2.06,2.08(4s,each3H,4OCOCH3), 3.84-3.88(m, 1H, H-5), 4.18(dd, J=12.4Hz, 4.2Hz, 1H, H-6a), 4.29(dd, J=12.4Hz, 5.2Hz, 1H, H-6b), 4.64 (s, 2H, ArCH2OH), 5.07(d, J=7.2Hz, 1H, H-1), 5.16(t, J=9.6Hz, 1H, H-4), 5.24-5.32(m, 2H, H-2, H-5), 6.98(d, J=8.4Hz, 2H, Ar-H), 7.27-7.31(m, 2H, Ar-H).
By above-mentioned prepared 4-hyd roxymethyl phenyl-O-β-D-2, 3, 4, 6-tetra--O-acetyl group pyranglucoside (20mmol, 9.08g) dissolve in 50ml dry methylene chloride, add acid binding agent triethylamine (22mmol, 2.22g), (21mmol is dripped under ice bath, 5.38g) 3, 4-diacetoxy Benzenecarbonyl chloride. is at the solution of 10ml dichloromethane, finish, remove ice bath, room temperature reaction 2 hours, reactant mixture is successively with water, saturated common salt water washing, separate dichloromethane layer, concentrating under reduced pressure obtains light yellow solid, white crystal 12.4g is obtained with dehydrated alcohol recrystallization, yield 92.1%, fusing point 57-58 DEG C.1HNMR(400MHz,CDCl3)d2.03,2.04,2.7,2.08(4s,each3H,4OCOCH3),2.32(s,6H,ArOAc),3.85(ddd,J=10.0,5.4,2.0Hz,1H),4.18(dd,J=12.4,2.4Hz,1H),4.27(dd,J=12.4,5.4Hz,1H),5.08(d,J=7.3Hz,1H),5.17(t,J=9.5Hz,1H),5.24-5.33(m,2H),5.31(s,2H),7.02(d,J=8.6Hz,2H),7.29(d,J=8.5Hz,1H),7.36(d,J=8.6Hz,2H),7.85(d,J=1.9Hz,1H),7.98
(dd,J=8.5,1.9Hz,1H)。
By above-mentioned prepared 4-(3; 4-diacetoxy benzoyloxymethy)-phenyl O-β-D-2,3,4; 6-tetra--O-acetyl group pyranglucoside 6(15mmol; 10.1g) dissolve in 50ml absolute methanol, add catalytic amount Dibutyltin oxide (0.5mmol, 0.125g) heating reflux reaction 3 hours; concentrating under reduced pressure; residue dehydrated alcohol-chloroform mixed solvent recrystallization (chloroform: dehydrated alcohol 8:1) obtains white crystal 5.76g, yield 92%, fusing point 203-204 DEG C.1HNMR(400MHz,CD3OD)d3.32-3.48(m,4H),3.68(dd,J=12.1,5.4Hz,1H),3.89(dd,J=12.1,2.1Hz,1H),4.91(m,1H),6.79(d,J=8.1Hz,1H),7.12(d,J=8.8Hz,2H),7.38(d,J=8.8Hz,2H),7.42(m,2H)。
Embodiment 2
By 2; 3; 4; 6-tetra--O-acetyl group-α-D-bromo Glucopyranose. (0.1mol; 41g) it is dissolved in 100 milliliters of dry DMF, adds p-Hydroxybenzylalcohol (0.12mol, 7.47g) and Anhydrous potassium carbonate (0.24mol; 16.6g); adding the cesium chloride of catalytic amount (5mmol, 0.84g), 40 DEG C are reacted 2 hours; reactant mixture is poured in frozen water; precipitating out white solid, collect by filtration white solid, gained white solid dehydrated alcohol recrystallization obtains white crystal 33.3g; yield 73%, fusing point 108.1-109.4 DEG C.
By above-mentioned prepared 4-hyd roxymethyl phenyl-O-β-D-2, 3, 4, 6-tetra--O-acetyl group pyranglucoside (0.04mol, 18.16g) dissolve in 100ml dry methylene chloride, add acid binding agent triethylamine (0.45mol, 4.45g), (0.42mol is dripped under ice bath, 10.76g) 3, 4-diacetoxy Benzenecarbonyl chloride. is at the solution of 15ml dichloromethane, finish, remove ice bath, room temperature reaction 2 hours, reactant mixture is successively with water, saturated common salt water washing, separate dichloromethane layer, concentrating under reduced pressure obtains light yellow solid, white crystal 24.8g is obtained with dehydrated alcohol recrystallization, yield 92.4%, fusing point 57-58 DEG C.
By above-mentioned prepared 4-(3; 4-diacetoxy benzoyloxymethy)-phenyl O-β-D-2,3,4; 6-tetra--O-acetyl group pyranglucoside 6(0.3mol; 20.2g) dissolve in 100ml absolute methanol, add catalytic amount Dibutyltin oxide (1mmol, 0.25g) heating reflux reaction 3 hours; concentrating under reduced pressure; residue dehydrated alcohol-chloroform mixed solvent recrystallization (chloroform: dehydrated alcohol 8:1) obtains white crystal 11.56g, yield 92.3%, fusing point 203-204 DEG C.
Claims (3)
1. the method for chemosynthesis 4-(3,4-dihydroxybenzoyl oxygen methyl)-phenyl-O-β-D-pyranglucoside, its step is as follows:
1) by 2,3,4; 6-tetra--O-acetyl group-α-D-bromo Glucopyranose. with to hydroxy-benzyl alcohol in dry dipolar aprotic solvent, under the catalysis of Anhydrous potassium carbonate and cesium chloride accelerator prepare 4-hyd roxymethyl phenyl-O-β-D-2,3; 4,6-tetra--O-acetyl group pyranglucoside；
2) by step 1) the 4-hyd roxymethyl phenyl-O-β-D-2 that obtains; 3; 4; 6-tetra--O-acetyl group pyranglucoside and 3,4-diacetoxy Benzenecarbonyl chloride .s are obtained by reacting 4-(3,4-diacetoxy benzoyloxymethy)-phenyl O-β-D-2 in dry methylene chloride with acid binding agent; 3; 4,6-tetra--O-acetyl group pyranglucoside, described acid binding agent is triethylamine；
3) by step 2) 4-(3 that obtains; 4-diacetoxy benzoyloxymethy)-phenyl-O-β-D-2; 3; 4; the Acetyl Protecting Groups that 6-tetra--O-acetyl group pyranglucoside is sloughed on sugar ring and phenyl ring in absolute methanol under the catalysis of stannum type oxide obtains target product 4-(3,4-dihydroxybenzoyl oxygen methyl)-phenyl-O-β-D-pyranglucoside.
2. chemosynthesis 4-(3 according to claim 1,4-dihydroxybenzoyl oxygen methyl) method of-phenyl-O-β-D-pyranglucoside, it is characterized in that the dipolar aprotic solvent used in the reaction of step 1) is acetone, DMF and dimethyl sulfoxide.
3. the method for chemosynthesis 4-according to claim 1 (3,4-dihydroxybenzoyl oxygen methyl)-phenyl-O-β-D-pyranglucoside, is characterized in that the stannum type oxide used in the reaction of step 3) is Dibutyltin oxide.
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