- Rapid biosynthesis of phenolic glycosides and their derivatives from biomass-derived hydroxycinnamates
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Biomass-derived hydroxycinnamates (mainly includingp-coumaric acid and ferulic acid), which are natural sources of aromatic compounds, are highly underutilized resources. There is a need to upgrade them to make them economically feasible. Value-added phenolic glycosides and their derivatives, both belonging to a class of plant aromatic natural products, are widely used in the nutraceutical, pharmaceutical, and cosmetic industries. However, their complex aromatic structures make their efficient biosynthesis a challenging process. To overcome this issue, we created three novel synthetic cascades for the biosynthesis of phenolic glycosides (gastrodin, arbutin, and salidroside) and their derivatives (hydroquinone, tyrosol, hydroxytyrosol, and homovanillyl alcohol) fromp-coumaric acid and ferulic acid. Moreover, because the biomass-derived hydroxycinnamates directly provided aromatic units, the cascades enabled efficient biosynthesis. We achieved substantially high production rates (up to or above 100-fold enhancement) relative to the glucose-based biosynthesis. Given the ubiquity of the aromatic structure in natural products, the use of biomass-derived aromatics should facilitate the rapid biosynthesis of numerous aromatic natural products.
- Zhao, Mingtao,Hong, Xulin,Abdullah,Yao, Ruilian,Xiao, Yi
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p. 838 - 847
(2021/02/09)
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- Gastrodin refining method
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The invention discloses a method for refining gastrodin. The method comprises the following step of: converting impurities shown in a formula I in a gastrodin crude product into gastrodin through an aldehyde compound, wherein the aldehyde compound is a formaldehyde aqueous solution or paraformaldehyde. The method has the advantages of being more economical, environmentally friendly, effective, safe and convenient to operate and higher in industrial adaptability. In addition, the problem of genotoxic impurity I existing in the current gastrodin raw material medicine can be effectively solved. For the gastrodin refined by the method, through HPLC detection, the content is 99.84-99.96%, the impurity I is not detected, and the total yield is 78.2%-81.6%; compared with gastrodin refined by 95%ethanol and sodium borohydride method, through the HPLC detection, the content is 98.91%, the impurity I content is 0.08%, and the total yield is 62.6%. The gastrodin refined by the method is high andstable in yield and basically consistent in batch-to-batch purity, and the impurity I can be completely removed.
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Paragraph 0007-0008; 0019; 0024-0035
(2020/11/12)
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- Synthesis method and application of gastrodin semihydrate
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The invention belongs to the technical field of bulk drug synthesis, and particularly relates to a synthesis method of gastrodin semihydrate. The synthesis method of the gastrodin semihydrate comprises a step of reacting 2-bromo-alpha-D-glucose tetraacetate with 4-hydroxymethylphenol in the presence of an alkali, a phase transfer catalyst, water and an organic solvent so as to obtain the gastrodinsemihydrate. The synthesis method is reasonable in reaction route, simple and feasible in operation process, high in the yield and purity of the gastrodin semihydrate, reasonable in cost and more beneficial for industrial production of the gastrodin semihydrate.
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Paragraph 0066-0088
(2020/05/01)
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- Transformation mechanisms of chemical ingredients in steaming process of gastrodia elata blume
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To explore the transformation mechanisms of free gastrodin and combined gastrodin before and after steaming of Gastrodia elata (G. elata), a fresh G. elata sample was processed by the traditional steaming method prescribed by Chinese Pharmacopoeia (2015 version), and HPLC-ESI-TOF/MS method was used to identify the chemical composition in steamed and fresh G. elata. Finally, 25 components were identified in G. elata based on the characteristic fragments of the compounds and the changes of the 25 components of fresh and steamed G. elata were compared by the relative content. Hydrolysis experiments and enzymatic hydrolysis experiments of 10 monomer compounds simulating the G. elata steaming process were carried out for the first time. As a result, hydrolysis experiments proved that free gastrodin or p-hydroxybenzyl alcohol could be obtained by breaking ester bond or ether bond during the steaming process of G. elata. Enzymatic experiments showed that steaming played an important role in the protection of gastrodin, confirming the hypothesis that steaming can promote the conversion of chemical constituents of G. elata—inhibiting enzymatic degradation. This experiment clarified the scientific mechanism of the traditional steaming method of G. elata and provided reference for how to apply G. elata decoction to some extent.
- Li, Yun,Liu, Xiao-Qian,Liu, Shan-Shan,Liu, Da-hui,Wang, Xiao,Wang, Zhi-Min
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- Synthesis method of gastrodin
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The invention discloses a synthesis method of gastrodin. The synthesis method of the gastrodin comprises the following steps: putting 4-formylphenyl-2,3,4,6-tetra-0-acetyl-beta-D-glucopyranoside and a reducing agent into a solvent, and conducting reaction at 0 to 30 DEG C for 0 to 3 hours; after complete reaction, adding water and performing quenching reaction; separating and taking an organic phase, concentrating the organic phase under the vacuum condition, and adding methanol in amount which is 2 to 5 times that of the organic phase; adding organic amine, performing refluxing reaction and performing alcoholysis; after complete reaction, adding activated carbon to decolor, filtering, concentrating, crystallizing and drying. By adoption of the synthesis method provided by the invention, the processes of the production process are reduced, and the method is safe, simple and convenient in operation, low in cost, low in pollution and suitable for large-scale production; furthermore, the prepared gastrodin product has stable quality and the purity is 99.9 percent or higher.
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Paragraph 0031; 0032; 0033; 0034
(2017/07/19)
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- A 4 - hydroxy methyl phenyl - beta - D glucopyranoside synthesis method (by machine translation)
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A 4 - hydroxy methyl phenyl - beta - D glucopyranoside synthetic method, comprises the following steps, step 1. The glycosidation reaction: five acetyl glucose, cresol, montmorillonite, Lewis acid in an organic solvent in the glycosidation reaction, and getting the middle raw material 1, and then in order to methanol recrystallization; step 2. Oxidation reaction: step 1 obtained in the middle of the raw material 1 in an organic solvent is added, by nitric acid ammonium oxidation intermediate raw material 1 obtained after the aldehyde group of the intermediate raw material 2, and then the ethanol solution is recrystallized; step 3. Ester exchange and reduction reaction: the step 2 to obtain the intermediate raw material 2 with methanol catalyst under the action of the ester exchange reaction, to obtain the 4 - formyl phenyl - beta - D - glucopyranoside, adding the borohydride reduction, to obtain the final product; the invention effectively solves the current Gastrodin synthesis in present technology; with more economic, environmental protection, safe and convenient operation, industrialization with stronger adaptability characteristics. (by machine translation)
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- A high-purity, high-stability Gastrodin semi-synthetic method
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The invention discloses a semi-synthesis method for high-purity and high-stability gastrodin. The semi-synthesis method comprises the following steps: carrying out a reduction reaction by taking tetraacethyl as a raw material; concentrating and adding a suitable amount of water into concentrated liquid; filtering and drying to obtain acethyl gastrodin; recycling a filtering solution which is used as a mother solution a; adding an alcohol solvent into the acethyl gastrodin to carry out a reflowing reaction, and concentrating; repeatedly reflowing and concentrating to obtain a concentrated solution; adding a non-polar solvent and filtering; drying solids to obtain a gastrodin rough product; recycling a filtering solution which is used as a mother solution b; adding alcohol and/or an ester solvent into the rough product of gastrodin; heating and completely dissolving; filtering and separating out crystals to obtain a refined product of gastrodin; recycling a filtering solution which is used as a mother solution c; mixing the mother solution b and the mother solution c; filtering and drying to obtain the rough product of gastrodin; and refining to obtain the refined product of gastrodin. The acethyl gastrodin prepared by the semi-synthesis method disclosed by the invention is stable, can be directly used as a crude drug, and can also be used as an intermediate to synthesize the high-purity gastrodin; the semi-synthesis method for the high-purity and high-stability gastrodin is very good for meeting the clinical demands on gastrodin and acethyl gastrodin.
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Page/Page column 8; 12
(2017/05/13)
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- Gastrodin production process
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Disclosed is a gastrodin production process comprising the preparation of acetoxymethyl phenol, the preparation of pentacetyl gastrodin, and the preparation and refining of gastrodin, including: stirring hydroxybenzyl alcohol, glacial acetic acid and ethy
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Paragraph 0051; 0055; 0056-0059; 0066
(2017/01/17)
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- Gastrodin Gastrodin and method for the preparation of intermediates for the synthesis of
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The invention discloses a method for preparing a gastrodin intermediate compound III. The method comprises the following steps: (1) reducing an initial raw material compound I through hydrogen, and obtaining a compound II; (2) reacting the compound II with an acetylation reagent, and obtaining a crude product of a compound III; and (3) recrystallizing the compound III obtained in the step (2), and obtaining a crude product of the compound III. In addition, the invention also provides a method for synthesizing gastrodin. The compound III prepared by the method provided in the invention is easy to recrystallize and high in purity, and a high-purity gastrodin finished product can be obtained.
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Paragraph 0082
(2017/05/23)
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- Gastrodin suitable for industrial production of the high-efficiency high-yield preparation method
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The invention discloses a high-efficiency high-yield preparation method suitable for industrial production of gastrodin. The high-efficiency high-yield preparation method comprises the preparation and aftertreatment steps, and specifically comprises the following steps: by taking tetra-acyl as a raw materail, adding 2-50 times alcohol solvent at a volume weight ratio, heating to 45-100DEG C and performing reflux, adding a reducing agent and performing reduction reaction, stirring until the reaction solution does not develop red after dropwise adding of a developing agent, and stopping reaction, concentrating and recovering the alcohol solvent, and concentrating to be 1-3 times of the tetra-acyl in volume weight ratio; and performing quenching on the reducing agent through after reaction aftertreatment liquid, standing, removing impurities, crystalizing, filtering and/or drying to obtain a target product. On the basis of mature industrial route, the three synthesis reactions are reduced to two, a one-step technology is adopted, an intermediate is not required for separation and purification, so that the three synthesis steps in the synthesis technology are reduced into one, and the high-purity gastrodin meeting the national medicinal product standard can be obtained through one-step synthesis without refinement of the obtained gastrodin.
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Paragraph 0082; 0083; 0084; 0085
(2016/10/07)
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- Improved synthesis of gastrodin, a bioactive component of a traditional chinese medicine
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Highly practical, four-step synthesis of gastrodin was developed using penta- O-acetyl-β-D-glucopyranose and p-cresol as glycosyl donor and glycosyl acceptor, respectively, in 58.1% overall yield. As the initial step, the penta-O-acetyl-β-D-glucopyranose was treated with p-cresol in the presence of BF3 ?Et2O as catalyst to generate 4-methylphenyl 2,3,4,6-tetra-O-acetyl-β-D- -glucopyranoside in 76.3% yield. Further, this product was subjected to radical bromination with N-bromosuccinimide (NBS) to provide 4-(bromomethyl)phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside in 91% yield. Subsequently, reaction of 4-(bromomethyl)phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside with a solution of acetone and saturated aqueous sodium bicarbonate led to 4-(hydroxymethyl)phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside in 93% yield. Finally, global deprotection of 4-(hydroxymethyl)phenyl 2,3,4,6-tetra-O- -acetyl-β- D-glucopyranoside under Zemplen conditions furnished gastrodin in 90% yield. Compared to the previously reported methods, this protocol has the advantages of operational simplicity, chromatography-free separation, high overall yield, inexpensive and common reagents as well as less waste pollutants, rendering it an alternative suitable for industrial production.
- Li, Yu-Wen,Ma, Cui-Li
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p. 1205 - 1212
(2015/01/30)
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- Highly chemoselective hydrogenation of active benzaldehydes to benzyl alcohols catalyzed by bimetallic nanoparticles
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By using novel Pd/Ni bimetallic nanoparticles as a catalyst, the active benzaldehydes were hydrogenated to the corresponding benzyl alcohols as unique products in practical quantitative yields. The undesired catalytic hydrogenolysis of the benzyl alcohol was inhibited completely. By using this hydrogenation as a key step, the total synthesis of the natural product gastrodin was achieved with less total steps and a higher total yield.
- Liu, Chulong,Bao, Hailin,Wang, Dingsheng,Wang, Xinyan,Li, Yadong,Hu, Yuefei
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p. 6460 - 6462
(2015/11/16)
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- Enzymatic resolution of (RS)-1-phenylalkyl β-D-glucosides to (R)-1-phenylalkyl β-primeverosides and (S)-1-phenylalkyl β-D-glucosides via plant xylosyltransferase
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The stereoselective xylosylation of (RS)-1-phenylalkyl β-D-glucosides was investigated using plant xylosyltransferase isolated from cultured Catharanthus roseus cells. Enzymatic xylosylation of (RS)-1-phenylethyl β-D-glucoside afforded (R)-1-phenylethyl β
- Shimoda, Kei,Katsuragi, Hisashi
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experimental part
p. 2060 - 2065
(2010/10/21)
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- Molecular interactions between Barley and Oat β-glucans and phenolic derivatives
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Equilibrium dialysis, molecular modeling, and multivariate data analysis were used to investigate the nature of the molecular interactions between 21 vanillin-inspired phenolic derivatives, 4 bile salts, and 2 commercially available β-glucan preparations, Glucagel and PromOat, from barley and oats. The two β-glucan products showed very similar binding properties. It was demonstrated that the two β-glucan products are able to absorb most phenolic derivatives at a level corresponding to the absorption of bile salts. Glucosides of the phenolic compounds showed poor or no absorption. The four phenolic derivatives that showed strongest retention in the dialysis assay shared the presence of a hydroxyl group in para-position to a CHO group. However, other compounds with the same structural feature but possessing a different set of additional functional groups showed less retention. Principal component analysis (PCA) and partial least-squares regression (PLS) calculations using a multitude of diverse descriptors related to electronic, geometrical, constitutional, hybrid, and topological features of the phenolic compounds showed a marked distinction between aglycon, glucosides, and bile salt retention. These analyses did not offer additional information with respect to the mode of interaction of the individual phenolics with the β-glucans. When the barley β-glucan was subjected to enzyme degradation, the ability to bind some but not all of the phenolic derivatives was lost. It is concluded that the binding must be dependent on multiple characteristics that are not captured by a single molecular descriptor.
- Simonsen, Henrik Toft,Nielsen, Mette S.,Christensen, Niels J.,Christensen, Ulla,Cour, Thomas V. La,Motawia, Mohammed Saddik,Jespersen, Birthe P.M.,Engelsen, Soren B.,Moller, Birger Lindberg
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experimental part
p. 2056 - 2064
(2010/07/02)
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- Glycosidic constituents of the tubers of Gymnadenia conopsea
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Ten minor new glycosidic constituents (1-10), together with 10 known compounds, have been isolated from a neuroprotective fraction of an ethanolic extract of the tubers of Gymnadenia conopsea. The structures of 1-10 were determined using spectroscopic and chemical methods. The compounds isolated were evaluated for activity in in vitro assays for acetylcholine esterase and monoamine oxidase inhibitory activities.
- Zi, Jiachen,Li, Shuai,Liu, Mingtao,Gan, Maoluo,Lin, Sheng,Song, Weixia,Zhang, Yanling,Fan, Xiaona,Yang, Yongchun,Zhang, Jianjun,Shi, Jiangong,Di, Duolong
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experimental part
p. 799 - 805
(2009/04/04)
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- Structure and reactivity of glycosides: IV. Koenigs-Knorr synthesis of aryl β-D-glucopyranosides using phase-transfer catalysts
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A series of acetylated aryl β-D-glucopyranosides were prepared in 12-63% yields from tetra-O-acetyl-α-D-glycopyranosyl bromide and phenols containing acyl, formyl, and hydroxy substituents, and also from sterically hindered phenols in the two-phase system chloroform-aqueous alkali in the presence of triethylbenzylammonium chloride. Hydroxyethylated sucrose and dibenzo-18-crown-6 do not behave as phase-transfer catalysts in glycosylation of phenols. 2001 MAIK "Nauka/Interperiodica".
- Pavlov,Sokolov,Zakharov
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p. 1811 - 1814
(2007/10/03)
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- THE BITTER IRIDOIDS FROM VIBURNUM URCEOLATUM
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Four new bitter iridoid glucosides, including three bis-iridoids, were isolated from Viburnum urceolatum and their structures elucidated.They are composed of loganin or deoxyloganin as the aglucone esterified with either aromatic glucoside or with glucose in the 4-position.Key Word Index-Viburnum urceolatum; Caprifoliaceae; iridoids; urceloatoside A-D; bitter components.
- Hase, Tsunao,Takao, Hideki,Iwagawa, Tetsuo
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p. 1977 - 1982
(2007/10/02)
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