CN103665061A - Synthetic method for regioselectively-acetylated methyl-D-pyranosides - Google Patents
Synthetic method for regioselectively-acetylated methyl-D-pyranosides Download PDFInfo
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Abstract
A disclosed synthetic method for regioselectively-acetylated methyl-D-pyranosides comprises: at 60 DGE C, taking water as a solvent, mixing a methyl-D-pyranoside and tetramethylammonium hydroxide (an aqueous solution with a concentration of 25%), adding 1- acetylimidazole, reacting for 14-18 h, removing solvent under a reduced pressure, and separating by a column to obtain the glucoside derivative acetylized at 6th position. The method employs water as a solvent to replace pyridine or DMF in traditional methods, so that the reaction toxicity is substantially reduced, and the column separation yield is basically 52% or more; and additionally, the provided efficient green method for acetylizing methyl-D-pyranosides is not only simple in operation, mild in conditions and low in cost, but also green and environment-friendly, is accord with the develop requirements of current social, and has good application and develop prospect.
Description
Technical field
The invention belongs to the synthetic field of fine chemicals and carbohydrate chemistry, be specifically related to a kind of synthetic method of regioselectivity acetylize methyl D-pyranoside.
Background technology
In organic synthesis technology, for the reactant that has a plurality of similar reactive behavior locating points, selective protection is the severe challenge to synthetic chemist always.Especially many, there is biological significance and have in the compounds such as the synthetic oligosaccharides that are worth, polysaccharide, glycopeptide, sugar ester synthetic; because glycan molecule exists the similar hydroxyl of a plurality of character; in order positioningly to introduce glycosidic link and various functional group on sugar ring, must optionally protect other hydroxyls on sugar ring.Therefore, the protection of the regioselectivity of sugared hydroxyl is one of study hotspot during carbohydrate chemistry synthesizes always.
At present, acetylize is one of functional group's conversion reaction the most frequently used in organic synthesis, is also the most frequently used technology of protection carbohydrate hydroxyl simultaneously.In addition, carbohydrate acetylate is the starting raw material of synthetic more complicated glucide often, is widely used in the synthesizing of some naturally occurring glucosides, oligosaccharides, glycoconjugate.The most frequently used method of carbohydrate glycoloylization is as acylating reagent with volatile irritating diacetyl oxide or Acetyl Chloride 98Min.; with pyridine or DMF, make solvent; or add on this basis some pyridine derivates; as promotor fast reaction speed such as 4-(N, N)-Dimethylamino pyridine (DMAP) or 4-(1-pyrrolidyl) pyridines.Due to pyridine and DMF, to have toxicity high and very unpleasant, and post-reaction treatment is complicated.Therefore a kind of develop green high-efficient regioselectivity acetylize carbohydrate hydroxyl method is not only synthetic extremely important for carbohydrate chemistry, and has again great actual application value.
Summary of the invention
The object of the invention is to; a kind of synthetic method of regioselectivity acetylize methyl D-pyranoside is provided, is intended to solve prior art and in acetylation is selected in methyl D-pyranoside region, adopts the problems such as high boiling point, highly toxic organic reagent are serious as solvent and environmental pollution, complex operation.
In order to realize above-mentioned task, the present invention takes following technical solution:
A synthetic method for regioselectivity acetylize methyl D-pyranoside, is characterized in that, implements according to the following steps:
Step 1, at 60 ℃, will be added to the water after methyl D-pyranoside and the mixing of 25% tetramethyl ammonium hydroxide solution;
Step 2, adds 1-acetyl imidazole as acylating reagent, at 60 ℃, reacts after 14-18h, and removal of solvent under reduced pressure, obtains the acetylizad methyl D-pyranoside of specific site through post separation.
Above-mentioned methyl D-pyranoside is methyl-α-D-glucopyranoside, methyl-β-D-glucopyranoside, methyl-α-D-galactopyranoside, methyl-β-D-galactopyranoside, methyl-α-D-mannopyranose glycosides.
Above-mentioned specific site is 6 primary hydroxyls of glucosides.
A mole input amount for above-mentioned methyl D-pyranoside, 25% tetramethyl ammonium hydroxide solution and 1-acetyl imidazole is respectively: methyl D-pyranoside 1.0eq, 25% tetramethyl ammonium hydroxide solution 1.2eq, 1-acetyl imidazole 3.0eq.
Region provided by the invention selects the synthetic method of acetylize methyl D-pyranoside to have following advantage:
(1) solve prior art and in methyl D-pyranoside region, selected the problems such as in acetylation, solvent boiling point is high, poisonous, environmental pollution serious, complex operation.There is environmental friendliness, reaction conditions is gentle, easy and simple to handle, with low cost, yield is high, and solvent for use not only environmental protection but also the feature such as cheap and easy to get, efficient, meet the demand for development of society, has good application and development prospect.
(2) compared with the existing technology; in acetylizad process, use water as solvent and replaced conventional organic solvent DMF or pyridine etc.; greatly reduce reaction toxicity, this has not only significantly reduced the synthetic cost of carbohydrate acetylate, more gives the advantage of this synthesis technique environmental protection.Be friendly, simple efficient, the gentle green synthesis method of reaction conditions in a kind of border, after reaction column separation, yield, substantially all more than 52%, can be amplified to gram level preparative-scale productive rate more than 50%.
Accompanying drawing explanation
Fig. 1 is the operation chart of the synthetic method of regioselectivity acetylize methyl D-pyranoside of the present invention;
Fig. 2 is that acetylizad chemical equation is selected in methyl D-pyranoside hydroxyl region;
Below in conjunction with drawings and Examples, the present invention is described in further detail.
Embodiment
In order to make object of the present invention, technical scheme and advantage clearer; in following embodiment; the synthetic method of regioselectivity acetylize methyl D-pyranoside of the present invention is carried out according to Fig. 1 and Fig. 2; be to be understood that; following embodiment only, in order to explain the present invention, is not intended to limit the present invention.
Embodiment 1:
At 60 ℃; with water, 200 μ L make solvent; by methyl-α-D-glucopyranoside 50mg(1.0eq) and 25% tetramethyl ammonium hydroxide solution 114 μ L(1.2eq) mix and to add after; add again 1-acetyl imidazole 85.9mg(3.0eq); after reaction 18h; removal of solvent under reduced pressure, obtains 6 acetylizad methyl-α-D-Glucopyranose glycoside derivates, post isolated yield 52% through post separation.
Embodiment 2:
At 60 ℃; with water, 200 μ L make solvent; by methyl-β-D-glucopyranoside 50mg(1.0eq) and 25% tetramethyl ammonium hydroxide solution 114 μ L(1.2eq) mix and to add after; add again 1-acetyl imidazole 85.9mg(3.0eq); after reaction 14h; removal of solvent under reduced pressure, obtains 6 acetylizad methyl-β-D-Glucopyranose glycoside derivates, post isolated yield 56% through post separation.
Embodiment 3:
At 60 ℃; with water, 200 μ L make solvent; by methyl-α-D-galactopyranoside 50mg(1.0eq) and Tetramethylammonium hydroxide (25% aqueous solution) 114 μ L(1.2eq) mix and to add after; add again 1-acetyl imidazole 85.9mg(3.0eq); after reaction 18h; removal of solvent under reduced pressure, obtains 6 acetylizad methyl-α-D-galactopyranose glycoside derivates, post isolated yield 59% through post separation.
Embodiment 4:
At 60 ℃; with water 200 μ L, make solvent by methyl-β-D-galactopyranoside 50mg(1.0eq) and 25% tetramethyl ammonium hydroxide solution 114 μ L(1.2eq) mix and to add after; add again 1-acetyl imidazole 85.9mg(3.0eq); after reaction 18h; removal of solvent under reduced pressure; through post separation, obtain 6 acetylizad methyl-β-D-galactopyranose glycoside derivates, post is separated produces 70%.
Embodiment 5:
At 60 ℃; with water, 200 μ L make solvent; by methyl-α-D-mannopyranose glycosides 50mg(1.0eq) and 25% tetramethyl ammonium hydroxide solution 114 μ L(1.2eq) mix and to add after; add again 1-acetyl imidazole 85.9mg(3.0eq); after reaction 18h; removal of solvent under reduced pressure, obtains 6 acetylizad methyl-α-D-mannopyranose glycoside derivates, post isolated yield 52% through post separation.
In above-described embodiment 1-5, green high-efficient regioselectivity acetylize experimental result is as shown in table 1:
Table 1: green high-efficient regioselectivity acetylize experimental result
Embodiment 6:
At 60 ℃; with water, 1.5mL makees solvent; by methyl-α-D-Glucopyranose glucosides 1.0g(1.0eq) and 25% tetramethyl ammonium hydroxide solution 2.3mL(1.2eq) mix and to add after; add 1-acetyl imidazole 852mg(1.5eq), after reaction 5h, then add 1-acetyl imidazole 1.134g(2.0eq); after reaction 12h; removal of solvent under reduced pressure, obtains 6 acetylizad methyl-α-D-Glucopyranose glycoside derivates, post isolated yield 50% through post separation.
Take embodiment 6 as example; after methyl-β-D-glucopyranoside, methyl-α-D-galactopyranoside, methyl-β-D-galactopyranoside, methyl-α-D-mannopyranose glycosides are amplified to gram level, the acetylize methyl D-pyranoside derivative productive rate obtaining is all greater than 50%.
Above embodiment is only preferred embodiment, the invention is not restricted to above-described embodiment, all any modifications of doing within the spirit and principles in the present invention, is equal to and replaces and improvement etc., within all should being included in protection scope of the present invention.
Claims (4)
1. a synthetic method for regioselectivity acetylize methyl D-pyranoside, is characterized in that, specifically implements according to the following steps:
Step 1, at 60 ℃, will be added to the water after methyl D-pyranoside and the mixing of 25% tetramethyl ammonium hydroxide solution;
Step 2, adds 1-acetyl imidazole as acylating reagent, at 60 ℃, reacts after 14-18h, and removal of solvent under reduced pressure, obtains the acetylizad methyl D-pyranoside of specific site through post separation.
2. the method for claim 1, it is characterized in that, described methyl D-pyranoside is methyl-α-D-glucopyranoside, methyl-β-D-glucopyranoside, methyl-α-D-galactopyranoside, methyl-β-D-galactopyranoside or methyl-α-D-mannopyranose glycosides.
3. the method for claim 1, is characterized in that, described specific site is 6 primary hydroxyls of glucosides.
4. the method for claim 1; it is characterized in that; a mole input amount for described methyl D-pyranoside, 25% tetramethyl ammonium hydroxide solution and 1-acetyl imidazole is respectively: methyl D-pyranoside is 1.0eq, and 25% tetramethyl ammonium hydroxide solution is that 1.2eq, 1-acetyl imidazole are 3.0eq.
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| US3022289A (en) * | 1959-02-13 | 1962-02-20 | Staley Mfg Co A E | Acylation of starch |
| US4137401A (en) * | 1975-07-08 | 1979-01-30 | Chembiomed Limited | Glycoside-ether-ester compounds |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3022289A (en) * | 1959-02-13 | 1962-02-20 | Staley Mfg Co A E | Acylation of starch |
| US4137401A (en) * | 1975-07-08 | 1979-01-30 | Chembiomed Limited | Glycoside-ether-ester compounds |
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| PRALHAD A. GANESHPURE, GIGI GEORGE, JAGANNATH DAS.: "Brønsted acidic ionic liquids derived from alkylamines as catalysts and mediums for Fischer esterification: Study of structure–activity relationship.", 《JOURNAL OF MOLECULAR CATALYSIS A: CHEMICAL》 * |
| PRALHAD A. GANESHPURE, GIGI GEORGE, JAGANNATH DAS.: "Brønsted acidic ionic liquids derived from alkylamines as catalysts and mediums for Fischer esterification: Study of structure–activity relationship.", 《JOURNAL OF MOLECULAR CATALYSIS A: CHEMICAL》, vol. 279, 10 July 2007 (2007-07-10), pages 182 - 186 * |
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