CN117229247A - Synthesis method of high-activity glass color factor - Google Patents
Synthesis method of high-activity glass color factor Download PDFInfo
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- CN117229247A CN117229247A CN202211324776.XA CN202211324776A CN117229247A CN 117229247 A CN117229247 A CN 117229247A CN 202211324776 A CN202211324776 A CN 202211324776A CN 117229247 A CN117229247 A CN 117229247A
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- 238000001308 synthesis method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 16
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 14
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 14
- 239000002841 Lewis acid Substances 0.000 claims abstract description 11
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 20
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 20
- 239000012074 organic phase Substances 0.000 claims description 18
- 239000011347 resin Substances 0.000 claims description 14
- 229920005989 resin Polymers 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000000706 filtrate Substances 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 230000002194 synthesizing effect Effects 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 239000008346 aqueous phase Substances 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 239000005457 ice water Substances 0.000 claims description 9
- 238000001704 evaporation Methods 0.000 claims description 8
- 238000006722 reduction reaction Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 239000003957 anion exchange resin Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000000967 suction filtration Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- 235000005074 zinc chloride Nutrition 0.000 claims description 3
- 239000011592 zinc chloride Substances 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 abstract description 2
- 239000004327 boric acid Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000010511 deprotection reaction Methods 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 235000019614 sour taste Nutrition 0.000 abstract 1
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 6
- KOGFZZYPPGQZFZ-QVAPDBTGSA-N (2s,3r,4s,5r)-2-(2-hydroxypropyl)oxane-3,4,5-triol Chemical compound CC(O)C[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O KOGFZZYPPGQZFZ-QVAPDBTGSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 102100035140 Vitronectin Human genes 0.000 description 4
- 108010031318 Vitronectin Proteins 0.000 description 4
- 229920001429 chelating resin Polymers 0.000 description 4
- 238000004811 liquid chromatography Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000002537 cosmetic Substances 0.000 description 3
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- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 239000007859 condensation product Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
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- 239000000049 pigment Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical group CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003741 xylose derivatives Chemical class 0.000 description 1
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- Saccharide Compounds (AREA)
Abstract
The invention relates to a synthesis method of high-activity glass color factor, belonging to the field of organic synthesis. According to the invention, 3, 4-dihydroxyketal of C-beta-D-xylopyranoside-2-acetone is dissolved in an organic solvent, sodium borohydride can preferentially reduce 7-ketocarbonyl of the 3, 4-dihydroxyketal into hydroxyl of S configuration in the presence of Lewis acid, and finally, a raw material of the vitreogene with high (beta, S) isomer content can be obtained after deprotection, wherein the proportion range of (beta, S)/(beta, R) isomer is 75:25 to 63:37. the product obtained by the method has good chemical purity, low residual quantity of boric acid, no acetic acid involved in the reaction process and no sour taste.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of high-activity glass color factor.
Background
The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art.
The name of vitrein (Pro-Xylane), english International cosmetic name (INCI) is "Hydroxypropyl tetrahydropyrantriol", i.e. hydroxypropyl tetrahydropyran triol, and its chemical structure is C-beta-D-xylopyranoside-2-hydroxypropane (formula I). The vitriol is a xylose derivative with the functions of beautifying and resisting wrinkles, which is discovered by Euler corporation, and can strengthen the connectivity of dermis and epidermis by promoting the generation of intercellular mucopolysaccharide, reconstructing the cell structure and improving the bonding capability of the dermis and the epidermis, thereby achieving the effects of beautifying and resisting wrinkles.
Patent WO 02051828 discloses its chemical structure, preparation and use in cosmetics.
Studies have shown that the stereochemical characteristics of vitronectin have an important influence on its biological activity, wherein the β -glycosidic bond in the 1-position is necessary to maintain the biological activity of vitronectin. The chemically synthesized vitriol is beta-type for the glycosidic bond of hydroxypropyl tetrahydropyran triol. Since the 7-position in the aglycone (i.e. the hydroxypropane side chain) is a chiral carbon, there are two diastereomers, namely C- β -D-xylopyranoside-7- (S) -hydroxypropane and C- β -D-xylopyranoside-7- (R) -hydroxypropane (hereinafter abbreviated as (β, S) and (β, R)). Cavezza A. Et al, synthesis of Pro-Xylane TM :A new biologically active C-glycoside in aqueous media，Bioorganic&Medicinal Chemistry Letters,2009,19 (3): 845-849 discloses a process for the chemical synthesis of vitrein, reducing C-beta-D-xylopyranoside-2-propanone with sodium borohydride in water gives a product with a ratio of (beta, S)/(beta, R) (i.e. formula III to formula IV, see formula 1) close to 1:1, and reducing C-beta-D-xylopyranoside-2-propanone with sodium borohydride in an isopropanol-acetic acid mixture gives a stereoisomer of the (beta, S) configuration with a de value of 90% (formula 2), i.e. a ratio of (beta, S)/(beta, R) of 95:5, a step of; while NaBH (OAc) is used in isopropanol 3 The reduction of C-beta-D-xylopyranoside-2-propanone also gives a stereoisomer of the (beta, S) configuration with a de value of 92%, i.e. a ratio of (beta, S)/(beta, R) of 96:4.
de values represent diastereomeric excess values (diastereomeric excess), describing the composition of a mixture of diastereomers, which is the excess value of one diastereomer to another diastereomer, calculated as follows:
d1 and D2 represent the mole fractions of the two diastereomers, respectively, of the product.
The studies by Cavezza a. Et al show that the ratio of (β, S)/(β, R) in hydroxypropyl tetrahydropyran triol has a significant effect on its biological activity, and that the biological activity of a mixture having a ratio of (β, S)/(β, R) of 70:30 is better than that of a mixture having a ratio of (β, S)/(β, R) of 1:1. Cavezza A. And other synthetic modes are that sodium borohydride is adopted to reduce C-beta-D-xylopyranoside-2-acetone, but because the C-beta-D-xylopyranoside-2-acetone contains three hydroxyl groups, the three hydroxyl groups react with sodium borohydride to consume a large amount of sodium borohydride, and meanwhile, the three hydroxyl groups can coordinate with boron atoms, and the adjacent diol has good stability in coordination mode, so that the boron atoms are not easy to remove. The inventor researches on the synthesis mode show that according to the synthesis mode, 1.8eq of sodium borohydride is needed for complete conversion of raw materials, and the sodium borohydride has higher price, so that the production cost is greatly increased; in addition, the boron content in the product synthesized by the method is very high, so that the burning residue is very high, and the quality requirement cannot be met.
In addition, the existing reduction technology adjusts the isomer ratio by adding acetic acid, but it is difficult to completely remove acetic acid or acetic acid by-products generated by the reaction, so that the commercial products generally have sour taste of acetic acid, which affects the smell and use comfort of cosmetics. Therefore, development of a suitable reduction process to produce a vitronectin starting material having a higher content of the (β, S) isomer than the (β, R) isomer is a problem to be solved.
Disclosure of Invention
Based on the technical background, the invention aims to provide a synthesis method of high-activity vitrein, which is characterized in that sodium borohydride is used for reducing 3, 4-dihydroxyketal of C-beta-D-xylopyranoside-2-acetone in an organic solvent under the condition of Lewis acid. The ratio range of (beta, S)/(beta, R) isomer in the vitriol prepared by the method is close to 75:25 to 63:37, and the isomer ratio of the two configurations can be regulated and controlled by different Lewis acid and organic solvent combinations. The glassy pigment product obtained by the method has good chemical purity, low residual quantity of boric acid, no acetic acid involved in the reaction process, no bad smell and higher economic value.
The invention specifically provides the following technical scheme:
in a first aspect of the present invention, there is provided a method for synthesizing a highly active glass color factor consisting of C- β -D-xylopyranoside-7- (S) -hydroxypropane (β, S-isomer) and C- β -D-xylopyranoside-7- (R) -hydroxypropane (β, R-isomer), wherein the ratio of the (β, S)/(β, R) isomers is 80:20 to 60:40;
the synthesis method comprises the following steps:
mixing 3, 4-dihydroxyketal of C-beta-D-xylopyranoside-2-acetone, an organic solvent and Lewis acid, adding sodium borohydride into the solution for reduction, and then deprotecting to obtain the high-activity vitrein.
Preferably, the lewis acid is cerium chloride or zinc chloride; in addition, the molar ratio of Lewis acid to sodium borohydride is 0.02-1: 1, further 0.2 to 0.6:1.
preferably, in the above synthesis method, the ketal solution has a concentration of 0.1 to 1mol/L, more preferably 0.3 to 0.6mol/L, and the solvent is preferably a lower alcohol, dichloromethane or a mixture of both, wherein the lower alcohol is methanol, ethanol or isopropanol.
Preferably, the molar ratio of the 3, 4-dihydroxyketal of C-beta-D-xylopyranoside-2-propanone to sodium borohydride is 1:0.4-1:1.5.
Preferably, the temperature of the reduction reaction is 0 to 20 ℃, more preferably 5 to 15 ℃.
Preferably, the time of the reduction reaction is 1 to 5 hours, more preferably 2 to 3 hours.
In one embodiment of the present invention, the specific synthesis steps of the high-activity glass color factor are as follows: uniformly mixing an organic solvent, lewis acid and 3, 4-dihydroxyketal of C-beta-D-xylopyranoside-2-acetone, adding sodium borohydride under the ice water bath condition, and stirring for reaction for 1-5 h; after the reaction is finished, adding water to quench the reaction, separating out an organic phase, drying the organic phase by using anhydrous sodium sulfate, carrying out suction filtration, and concentrating the filtrate under reduced pressure to obtain an intermediate; dissolving the intermediate in methanol, adding p-toluenesulfonic acid, stirring at room temperature for reaction for 2-4 h, adding alkaline resin to adjust the pH of the reaction system to be neutral, filtering to remove the resin, and evaporating the methanol in the reaction system to obtain the high-activity vitriol factor (crude product).
Further, after the reduction reaction is finished, the aqueous phase part is extracted by ethyl acetate, and is combined with the organic phase part, washed and dried.
Further, the basic resin is a strongly basic anion exchange resin.
Further, the residue further comprises a purification step: adding water into the residue to dissolve to obtain a crude product aqueous solution, washing the aqueous solution by adopting ethyl acetate, adding active carbon to stir and decolor, and evaporating the decolored aqueous solution to dryness to obtain the high-activity vitreous color factor (pure product).
In the above synthetic method, the 3, 4-dihydroxyketal of C-beta-D-xylopyranoside-2-propanone has a structure as shown in formula V or formula VI:
the ketal compounds described above are preferably condensation products of C-beta-D-xylopyranoside-2-propanone with acetone or 2, 3-butanedione, possibly synthesized as follows:
the specific steps of the above route 1 are as follows:
to a 500mL reaction flask, 250mL of anhydrous acetone, 38 g (0.2 mol) of C-. Beta. -D-xylopyranoside-2-acetone, and 2.6 g (15 mmol) of p-toluenesulfonic acid were successively added, and the mixture was stirred at room temperature for 24 hours. After the reaction, acetone was distilled off under reduced pressure, 300mL of methylene chloride was added to dilute, 100mL of saturated sodium bicarbonate solution was used for washing once, saturated sodium chloride solution was used for washing once, anhydrous sodium sulfate was used for drying the organic phase, filtration was carried out, and the solvent was distilled off under reduced pressure from the filtrate to obtain crude 3, 4-dihydroxyketal of C-. Beta. -D-xylopyranoside-2-propanone (formula V).
The specific steps of the above route 2 are as follows:
a500 mL reaction flask was charged with 38 g (0.2 mol) of C-. Beta. -D-xylopyranoside-2-propanone, 300mL of methanol, 31 g (0.36 mol) of 2, 3-butanedione, 38.2 g (0.36 mol) of trimethyl orthoformate and 2.6 g (15 mmol) of p-toluenesulfonic acid, and the mixture was refluxed with stirring at 70℃for 24 hours. After the reaction, the solvent was distilled off under reduced pressure, and the residue was dissolved in 300mL of methylene chloride, washed once with 100mL of saturated sodium bicarbonate solution, washed once with saturated sodium chloride solution, and the organic phase was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure from the filtrate to give a crude product of 3, 4-dihydroxyketal of C-. Beta. -D-xylopyranoside-2-propanone (formula VI).
The beneficial effects of the above technical scheme are:
the vitriol is used as a raw material of cosmetics with higher economic value, and the activity and the isomer ratio of the vitriol have obvious correlation. The invention provides a synthesis method of a high-activity glass color factor product, wherein in the glass color factor product obtained by the preparation method, two isomers of C-beta-D-xylopyranoside-7- (S) -hydroxy propane (beta, S-isomer) and C-beta-D-xylopyranoside-7- (R) -hydroxy propane (beta, R-isomer) are in a high-activity proportion range.
Detailed Description
It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the present invention. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
In order to enable those skilled in the art to more clearly understand the technical scheme of the present invention, the technical scheme of the present invention will be described in detail with reference to specific embodiments.
Example 1
200mL of methylene chloride, 50mL of methanol, 23.0 g (0.1 mol) of 3, 4-dihydroxyketal (V) of C-beta-D-xylopyranoside-2-acetone and 9.9 g (0.04 mol) of cerium chloride are sequentially added into a 500mL reaction bottle, 3.0 g (0.08 mol) of sodium borohydride is slowly added under the condition of ice water bath temperature control of 5-10 ℃, and the reaction is stirred for 2.5h. After the reaction was completed, 200mL of water was slowly added under stirring in an ice-water bath, stirring was performed at room temperature for 1 hour, the organic phase was separated, the aqueous phase was extracted 2 times with 100mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, suction-filtered, and the filtrate was concentrated under reduced pressure to dryness. Dissolving the obtained intermediate in 100mL of methanol, adding 2 g of p-toluenesulfonic acid, stirring for dissolution, reacting for 3 hours at room temperature, adding alkaline resin (Amberlite 711 strong alkaline anion exchange resin), adjusting the pH value to 7.0, filtering to remove the resin, evaporating the filtrate under reduced pressure to remove the methanol, adding 100mL of water for dissolving the residue, washing with 100mL of ethyl acetate for 2 times, adding 1.5 g of active carbon into the aqueous solution, stirring for decoloration for 60 minutes at room temperature, filtering, evaporating the aqueous phase under reduced pressure to obtain 15.3 g of vitrein with the purity of 98.8%, and the total yield of 79% in two steps6%. The ratio of the (β, S) to (β, R) isomers was 70:30 as determined by liquid chromatography. MS (ESI) M/z 193.0[ (M+H) + ]。 1 H NMR(400MHz,D 2 O)：4.04-3.95(m,1H),3.92-3.87(m,1H),3.60-3.53(m,1H),3.39-3.10(m,4H),1.93-1.85(m,1H),1.65-1.58(m,0.7H),1.51-1.44(m,0.3H),1.19-1.14(m,3H)。
Example 2
200mL of methylene chloride, 50mL of methanol, 30.4 g (0.1 mol) of 3, 4-dihydroxyketal (VI) of C-beta-D-xylopyranoside-2-acetone and 9.9 g (0.04 mol) of cerium chloride are sequentially added into a 500mL reaction bottle, 3.0 g (0.08 mol) of sodium borohydride is slowly added under the condition of ice water bath temperature control of 5-10 ℃, and the reaction is stirred for 3h. After the reaction was completed, 200mL of water was slowly added under stirring in an ice-water bath, stirring was performed at room temperature for 1 hour, the organic phase was separated, the aqueous phase was extracted 2 times with 100mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, suction-filtered, and the filtrate was concentrated under reduced pressure to dryness. The intermediate obtained was dissolved in 100mL of methanol, 2 g of p-toluenesulfonic acid was added, stirred and dissolved, reacted at room temperature for 3 hours, alkaline resin (Amberlite 711 strongly basic anion exchange resin) was added, the pH was adjusted to 7.0, the resin was removed by filtration, the methanol was distilled off under reduced pressure, the residue was dissolved in 100mL of water, washed with 100mL of ethyl acetate for 2 times, 1.5 g of activated carbon was added to the aqueous solution, stirred and decolorized at room temperature for 60 minutes, suction filtration and distilled off under reduced pressure to dryness of the aqueous phase, 15.0 g of vitrine was obtained, purity was 98.6%, and total yield of two steps was 78%. The ratio of the (beta, S) to (beta, R) isomers was 65:35 as determined by liquid chromatography. MS (ESI) M/z 193.0[ (M+H) + ]。 1 H NMR(400MHz,D 2 O)：4.04-3.95(m,1H),3.92-3.87(m,1H),3.60-3.53(m,1H),3.39-3.10(m,4H),1.93-1.86(m,1H),1.65-1.58(m,0.65H),1.50-1.44(m,0.35H),1.19-1.14(m,3H)。
Example 3
To a 500mL reaction flask, 150mL of methylene chloride, 100mL of methanol, 23.0 g (0.1 mol) of 3, 4-dihydroxyketal (V) of C-. Beta. -D-xylopyranoside-2-propanone and 5.3 g (0.04 mol) of zinc chloride were sequentially added, and 2.6 g (0.07 mol) of sodium borohydride was slowly added under the condition of controlling the temperature of the ice water bath to 10 to 15℃and the reaction was stirred for 3 hours. After the reaction was completed, 200mL of water was slowly added under stirring in an ice-water bath, stirring was performed at room temperature for 1 hour, the organic phase was separated, the aqueous phase was extracted 2 times with 100mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, suction-filtered, and the filtrate was concentrated under reduced pressure to dryness. The intermediate obtained was dissolved in 100mL of methanol, 2 g of p-toluenesulfonic acid was added, stirred and dissolved, reacted at room temperature for 3 hours, alkaline resin (Amberlite 711 strongly basic anion exchange resin) was added, the pH was adjusted to 7.0, the resin was removed by filtration, the methanol was distilled off under reduced pressure, the residue was dissolved in 100mL of water, washed with 100mL of ethyl acetate for 2 times, 1.5 g of activated carbon was added to the aqueous solution, stirred and decolorized at room temperature for 60 minutes, suction filtration and distilled off under reduced pressure to dryness of the aqueous phase, 15.4 g of vitrine was obtained, the purity was 98.8%, and the total yield of the two steps was 80%. The ratio of (β, S) to (β, R) isomers was 75:25 as determined by liquid chromatography. MS (ESI) M/z 193.0[ (M+H) + ]。 1 H NMR(400MHz,D 2 O)：4.04-3.95(m,1H),3.92-3.87(m,1H),3.60-3.53(m,1H),3.39-3.10(m,4H),1.93-1.85(m,1H),1.65-1.58(m,0.75H),1.51-1.45(m,0.25H),1.19-1.15(m,3H)。
Example 4
To a 500mL reaction flask, 250mL of methanol, 23.0 g (0.1 mol) of 3, 4-dihydroxyketal (V) of C-. Beta. -D-xylopyranoside-2-propanone, and 9.9 g (0.04 mol) of cerium chloride were sequentially added, and 3.0 g (0.08 mol) of sodium borohydride was slowly added under the condition of controlling the temperature of the ice water bath to 10-15℃and stirred for 3 hours. After the reaction was completed, 200mL of water was slowly added under ice bath stirring, stirring was performed at room temperature for 1 hour, the organic phase was separated, the aqueous phase was extracted 2 times with 100mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, suction-filtered, and the filtrate was concentrated under reduced pressure to dryness. Dissolving the obtained intermediate in 100mL of methanol, adding 2 g of p-toluenesulfonic acid, stirring for dissolving, reacting for 3h at room temperature,adding alkaline resin (Amberlite 711 strong alkaline anion exchange resin), regulating pH value to 7.0, filtering to remove resin, evaporating methanol from filtrate under reduced pressure, adding 100mL of water to dissolve residues, washing 2 times with 100mL of ethyl acetate, adding 1.5 g of active carbon into the water solution, stirring and decoloring for 60min at room temperature, filtering, evaporating water phase under reduced pressure to obtain 14.4 g of vitronectin with purity of 98.9%, and total yield of 75% in two steps. The ratio of the (β, S) to (β, R) isomers was 63:37 as determined by liquid chromatography. MS (ESI) M/z 193.0[ (M+H) + ]。 1 H NMR(400MHz,D 2 O)：4.04-3.95(m,1H),3.92-3.87(m,1H),3.60-3.53(m,1H),3.39-3.10(m,4H),1.93-1.85(m,1H),1.65-1.58(m,0.63H),1.51-1.44(m,0.37H),1.19-1.14(m,3H)。
Example 5
In this example, a method for preparing 3, 4-dihydroxyketal of C- β -D-xylopyranoside-2-propanone is provided:
the preparation method of the compound shown in the formula V comprises the following steps:
to a 500mL reaction flask, 250mL of anhydrous acetone, 38 g (0.2 mol) of C-. Beta. -D-xylopyranoside-2-acetone, and 2.6 g (15 mmol) of p-toluenesulfonic acid were successively added, and the mixture was stirred at room temperature for 24 hours. After the reaction, acetone was distilled off under reduced pressure, 300mL of methylene chloride was added to dilute, 100mL of saturated sodium bicarbonate solution was used for washing once, saturated sodium chloride solution was used for washing once, anhydrous sodium sulfate was used for drying the organic phase, filtration was carried out, and the filtrate was distilled off under reduced pressure to remove the solvent, thereby obtaining crude 3, 4-dihydroxyketal of C-beta-D-xylopyranoside-2-propanone represented by formula V.
A process for the preparation of a compound of formula VI:
a500 mL reaction flask was charged with 38 g (0.2 mol) of C-. Beta. -D-xylopyranoside-2-propanone, 300mL of methanol, 31 g (0.36 mol) of 2, 3-butanedione, 38.2 g (0.36 mol) of trimethyl orthoformate and 2.6 g (15 mmol) of p-toluenesulfonic acid, and the mixture was refluxed with stirring at 70℃for 24 hours. After the reaction, the solvent was distilled off under reduced pressure, and the residue was dissolved in 300mL of methylene chloride, washed once with 100mL of saturated sodium bicarbonate solution, washed once with saturated brine, and the organic phase was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure from the filtrate to obtain a crude product of 3, 4-dihydroxyketal of C-. Beta. -D-xylopyranoside-2-propanone of formula VI.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method for synthesizing high-activity glass color factor, which is characterized in that the high-activity glass color factor is composed of C-beta-D-xylopyranoside-7- (S) -hydroxy propane and C-beta-D-xylopyranoside-7- (R) -hydroxy propane, and the ratio of (beta, S)/(beta, R) isomer is 80:20-60:40;
the synthesis method comprises the following steps:
mixing 3, 4-dihydroxyketal of C-beta-D-xylopyranoside-2-acetone, an organic solvent and Lewis acid, adding sodium borohydride into the solution for reduction, and then deprotecting to obtain the high-activity vitrein.
2. The method for synthesizing high-activity glass color factor according to claim 1, wherein the Lewis acid is cerium chloride or zinc chloride; the molar ratio of the Lewis acid to the sodium borohydride is 0.02-1: 1.
3. the method for synthesizing high-activity glass color factor according to claim 1, wherein the concentration of the ketal solution is 0.1-1 mol/L, the solvent is preferably lower alcohol, dichloromethane or a mixture of the two, and the lower alcohol is methanol, ethanol or isopropanol.
4. The method for synthesizing high-activity glass color factor according to claim 1, wherein the molar ratio of the 3, 4-dihydroxyketal of the C-beta-D-xylopyranoside-2-acetone to the sodium borohydride is 1:0.4-1:1.5.
5. The method for synthesizing high-activity glass color factor according to claim 1, wherein the temperature of the reduction reaction is 0-20 ℃.
6. The method for synthesizing high-activity glass color factor according to claim 1, wherein the time of the reduction reaction is 1-5 hours.
7. The method for synthesizing the high-activity glass color factor according to any one of claims 1 to 6, which is characterized in that an organic solvent, lewis acid and 3, 4-dihydroxyketal of C-beta-D-xylopyranoside-2-acetone are uniformly mixed, sodium borohydride is added under the ice water bath condition, and stirring reaction is carried out for 1 to 5 hours; after the reaction is finished, adding water to quench the reaction, separating out an organic phase, drying the organic phase by using anhydrous sodium sulfate, carrying out suction filtration, and concentrating the filtrate under reduced pressure to obtain an intermediate; dissolving the intermediate in methanol, adding p-toluenesulfonic acid, stirring at room temperature for reaction for 2-4 h, adding alkaline resin to adjust the pH of the reaction system to be neutral, filtering to remove the resin, and evaporating the residue of the methanol in the reaction system to obtain the high-activity glass color factor.
8. The method for synthesizing high-activity glass color factor according to claim 7, wherein after the reduction reaction is finished, the aqueous phase part is extracted by ethyl acetate, and is combined with the organic phase part, washed and dried.
9. The method for synthesizing high-activity glass color factor according to claim 7, wherein the basic resin is a strongly basic anion exchange resin.
10. The method of synthesizing highly reactive glass color factor according to claim 7, wherein the residue further comprises a purification step of: and adding water into the residue to dissolve the residue to obtain a crude product aqueous solution, washing the aqueous solution by adopting ethyl acetate, adding active carbon to stir and decolor, and evaporating the decolored aqueous solution to dryness to obtain the high-activity vitreous color factor.
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