Alpha-arbutin intermediate, 1, 2-cis- indican derivate and stereoselective synthetic method

A technology of stereoselectivity and synthesis method, applied in the direction of sugar derivatives, organic chemistry, etc., can solve the problems of difficulty in the formation of aryl glycosides, a large number of synthesis restrictions, and high reaction conditions, achieve good application prospects, reduce synthesis steps, and simple preparation process. Effect

Inactive Publication Date: 2011-11-23
NANJING UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] 1) The aromatic ring has electric absorption, which leads to weak nucleophilicity of phenols in acidic conditions, and the power supply of the hydroxyl group on the benzene ring makes the aromatic ring of phenols also have considerable nucleophilicity ( figure 2 ), which leads to the generation of carbon glycosides, so the generation of aryl glycosides is more difficult than that of aliphatic glycosides;
[0006] 2) The preparation of fully protected or partially protected compounds with no adjacent groups participating in the C-2 position usually requires multi-step reactions, and the yield is low
Pd / C is required for the removal of benzyl group, the reaction conditions are high, and the large-scale synthesis is limited

Method used

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  • Alpha-arbutin intermediate, 1, 2-cis- indican derivate and stereoselective synthetic method
  • Alpha-arbutin intermediate, 1, 2-cis- indican derivate and stereoselective synthetic method
  • Alpha-arbutin intermediate, 1, 2-cis- indican derivate and stereoselective synthetic method

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preparation example Construction

[0037] combine image 3 , the stereoselective synthesis method of α-arbutin intermediate of the present invention, comprises the following steps:

[0038] (1) Add pentabenzoyl glucose donor (chemical structural formula: ) under nitrogen protection,

[0039]

[0040] Hydroquinone acceptor and solvent; wherein, the molar ratio of sugar group donor pentabenzoyl glucose to acceptor hydroquinone is 1:1.5~4, and the amount of solvent is 8~20 of pentabenzoyl glucose times; the solvent is dichloromethane, chloroform or toluene.

[0041] (2) After cooling to -5~5°C, add Lewis acid slowly under stirring and raise to room temperature. Among them, the Lewis acid is BF 3 ·Et 2 O, TMSOTf, AlCl 3 or FeCl 3 .

[0042] (3) Insulate and stir at 40-60°C for 24-72 hours.

[0043](4) the reaction mixture is separated through recrystallization or silica gel column, wherein the eluent separated by silica gel column is ethyl acetate and sherwood oil, and its volume ratio is ethyl acetate: ...

Embodiment 1

[0056] Example 1: Synthesis of p-hydroxyphenyl-2,3,4,6-tetra-O-benzoyl-D-glucoside

[0057] 1.1 Pentabenzoyl Glucose: Hydroquinone: BF 3 ·Et 2 O=1:2:4 (molar ratio), dichloromethane was refluxed for 48h.

[0058] Add 2.5g (3.6mmol) pentabenzoylglucose and 0.79g hydroquinone (7.2mmol) into a 50ml three-necked flask, fill with nitrogen protection, stir and cool to 0°C under ice bath, then add 25ml of dry Chloromethane and 1.9ml (14.4mmol) boron trifluoride ether solution, naturally warmed to room temperature within 2h, then heated to 40-50°C in an oil bath, and refluxed for 48h. After the reaction was completed, add 10ml of dichloromethane to dilute, stir with 20ml of ice water, then wash with 20ml×2 saturated sodium carbonate solution, 20ml of ice water, and dry the organic layer with anhydrous sodium sulfate, filter, evaporate the solvent to obtain a light yellow solid, The yield of crude product is 92%.

[0059] Take 1.3g of the crude product and separate it by silica gel...

Embodiment 2

[0064] Example 2: Synthesis of p-tert-butylphenyl-2,3,4,6-tetra-O-benzoyl-D-glucoside

[0065] Add 2.0g of pentabenzoylglucose and 0.86g of p-tert-butylphenol to a 50ml three-necked flask at room temperature, stir and cool to -5°C under ice bath, then add 20ml of dry dichloromethane and 1.52ml of trifluoro Boronium ether solution, naturally rose to room temperature within 2h, then heated to 40-50°C in an oil bath, and refluxed for 48h. After the reaction is completed, add 10ml of dichloromethane to dilute, stir with 20ml of ice water, then wash with 20ml×2 saturated sodium carbonate solution, 20ml of ice water, dry the organic layer with anhydrous sodium sulfate, filter, evaporate the solvent to obtain a light yellow syrup 2.17 g. Take 0.25g of the syrup and separate it through silica gel column chromatography (ethyl acetate:petroleum ether=1:4~1:2) to obtain 0.22g of glycosidation product with a glycosidation yield of 93%. 1 H-NMR confirmed the C-1 proton integration ratio ...

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Abstract

The invention discloses an alpha-arbutin intermediate, a 1, 2-cis-Piceid derivative and the stereo-selectivity synthetic method thereof. Under the condition of room temperature, the invention is added with pentabenzoylglucose donator, hydroquinone or a phenol derivative and a solvent, which is added with Lewis acid slowly under the condition of continuous stirring after being cooled, heated to room temperature, kept warm at a reflow temperature, stirred and reacts; reacting mixture is separated through recrystallization or silicagel column and the alpha-arbutin intermediate or the 1, 2-cis-Piceid derivative thereof is obtained through stereo-selectivity synthesis. The invention is synthesized from pentabenzoylglucose by single stage method and glycosyl donator is easy for obtaining; reaction is carried out under mild condition and low temperature is not needed; the stereo-selectivity of glycosyl synthesis is high; a polyphenol compound does need to protect other groups thereof and attends the reaction directly, which overcomes the malady of long technique route, reduces synthesis steps and lowers production cost.

Description

technical field [0001] The invention belongs to the technology of fine chemicals and sugar chemistry, in particular a novel method for stereoselectively synthesizing α-arbutin intermediates and 1,2-cis glycoside analogues thereof. Background technique [0002] Arbutin (β-arbutin, 1) is a natural product extracted from blueberry leaves. It has a wide range of uses. It can be used as a photo color stabilizer. It has certain diuretic and antiasthmatic effects. Its excellent whitening effect (Maeda K, Fukuda M. Arbutin: Mechanism of Its Depigmenting Action in Human Melanocyte Culture [J]. J Pharmacol. Exp. Ther., 1996, 276: 765-769) has been widely used in various cosmetics. Recently, the biological activity of α-arbutin (α-arbutin, 2) has attracted people's attention again, because its IC 50 = 2.1 Much lower than the IC of β-arbutin 50 ≥30, while having a strong tyrosine oxidase inhibitory effect, it inhibits the growth of normal cells less than β-arbutin (Sugimoto K, Nishimu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H15/203
Inventor 方韬丰巍伟方志杰
Owner NANJING UNIV OF SCI & TECH
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