62499-27-8

Basic information

• Product Name: Gastrodin
• Synonyms: 4-hydroxybenzyl alcohol 4-o-bata-d-glucoside;4-O-BETA-D-GLUCOPYRANOSYLOXYBENZYL ALCOHOL;(2R,3S,4S,5R,6S)-2-HYDROXYMETHYL-6-(4-HYDROXYMETHYL-PHENOXY)-TETRAHYDRO-PYRAN-3,4,5-TRIOL;GASTRODIN;Gastro enterical;Gastrodin ,98%;4-(Hydroxymethyl)phenyl β-D-glucopyranoside;4-(β-D-Glucopyranosyloxy)benzyl alcohol
• CAS NO: 62499-27-8
• Molecular Formula: C₁₃H₁₈O₇
• Molecular Weight: 286.28
• EINECS: 1806241-263-5
• Product Categories: Benzhydrols, Benzyl & Special Alcohols;Natural Plant Extract;APIS;Herb extract;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;natural product;Inhibitors
• Mol File: 62499-27-8.mol

Chemical Properties

• Melting Point: 169-170°
• Boiling Point: 563.2 °C at 760 mmHg
• Flash Point: 294.4 °C
• Appearance: /
• Density: 1.504 g/cm³
• Vapor Pressure: 1.6E-13mmHg at 25°C
• Refractive Index: 1.638
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly, Sonicated), Methanol (Slightly), Water (Slightly, Sonicated)
• PKA: 9.10(at 25℃)
• Merck: 14,4375
• CAS DataBase Reference: Gastrodin(CAS DataBase Reference)
• NIST Chemistry Reference: Gastrodin(62499-27-8)
• EPA Substance Registry System: Gastrodin(62499-27-8)

Safety Data

• RTECS: LZ5776885
• Hazardous Substances Data: 62499-27-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Applications:
Gastrodin is used as a pharmaceutical agent for its neuroprotective properties. It upregulates heme oxygenase-1 expression through the activation of the p38 MAPK/Nrf2 signaling pathway, thus protecting SH-SY5Y cells from MPP+-induced oxidative cell death.
Used in Traditional Chinese Medicine:
Gastrodin is used as a traditional Chinese medicinal ingredient for its various therapeutic effects. It is believed to expel wind, relieve convulsion, calm the liver, suppress liver-yang, and expel wind evil and channel due to its sweet flavor, liver channel tropism, and neutral nature.
Used in Chemical Research:
Gastrodin, being a white solid with specific physical and chemical properties, is used in chemical research for the study of its properties and potential applications in various fields.

History

It has been more than 30?years since the chemical composition of Gastrodia elata was analyzed. It includes phenols, organic acids, sterols, and so on. At present, the studies of the composition of Gastrodia elata focus on the fingerprint, but the studies of gastrodin were centered on the activity. The studies showed that gastrodin has many pharmacological effects with safety and few side effects; moreover, it is not easy to accumulate in the body. Based on traditional medicinal experience of Gastrodia elata, gastrodin has been developed as a medicine for the treatment of insomnia, headaches, and other symptoms related to the functions and indications of Gastrodia elata. At present, many pharmaceutical factories in China have produced active pharmaceutical ingredients (API) and general preparation of gastrodin, such as Gastrodia tablet, Gastrodia capsule, and Gastrodia injection. To reduce the frequency of administration, the fluctuations of blood drug concentration, as well as side effects, some new dosage forms have been developed in recent years, such as Gastrodia dispersible tablets, Gastrodia sustained-release tablet, sustained-release pellets and osmotic pump tablets, etc. . Although gastrodin has been applied clinically, a lot of studies still need to be done to confirm the pharmacological effects of gastrodin. Recent studies found that other compositions of Gastrodia elata also showed rather excellent biological activity, suggesting that the study of Gastrodia elata and gastrodin needs further investigation.

Indications

Gastrodin is included in the International Pharmacopoeia (5th ed.). The dosage forms include injections, tablets, and capsules. They are widely used for the treatment of vertigo (Meniere’s disease, medicinal dizziness, traumatic vertigo, sudden deafness, vestibular neuronitis, vertebrobasilar insufficiency, etc.), headache (vascular headache, migraine, etc.), neuralgia (trigeminal neuralgia, sciatica, etc.), neurasthenia syndrome, and brain traumatic syndrome .

Pharmacology

Gastrodin has the pharmacological effects of hypnosis, sedation, and anticonvulsive. The pentobarbital sodium-induced sleep time test and sodium barbital-induced sleep onset latency test demonstrated that gastrodin can prolong the sleeping time and shorten the sleep onset latency in mouse, suggesting that gastrodin has the sedative and hypnotic effects .Gastrodin also has antiepileptic effect. It suggested that gastrodin may inhibit the hippocampal excitatory neurotransmitter receptors of amino acid glutamate, activate hippocampal inhibitory neurotransmitter receptor of GABA, reduce the excitability of the cerebral cortex, and thus attenuate the development of epilepsy to play a role of antiepileptic effect .Additionally, research has shown that gastrodin has certain pharmacological effect on scavenging free radicals and inhibiting the central nerve cell apoptosis, etc., which may be related to antiaging and neural protection . According to the available references, the researches of pharmacology and clinical efficacy of gastrodin are very preliminary; more research evidences still need to confirm whether gastrodin is the active constituent of rhizoma gastrodiae.

Clinical Use

Gastrodin has sedative and hypnotic, analgesia, and immune enhancement function and is used for the treatment of tension headache to relieve pain and intense sentiment and thus further relieve the related symptoms . Clinical usage of gastrodin acupoint injection to treat insomnia also achieves certain effect . Moreover, gastrodin agents have been used for the treatment of cardiovascular diseases and microcirculation system, such as hypertension and coronary heart disease without obvious side effects .It is also reported that gastrodin can treat epilepsy, vascular dementia, deafness, tinnitus, herpes zoster, osteoarthritis, cognitive impairment, and so on but still needs further investigation.

InChI:InChI=1/C13H18O7/c14-5-7-1-3-8(4-2-7)19-13-12(18)11(17)10(16)9(6-15)20-13/h1-4,9-18H,5-6H2/t9-,10-,11+,12-,13-/m1/s1

Upstream product

• 64291-41-4 (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(4-(hydroxymethyl)phenoxy)-tetrahydro-2H-pyran-3,4,5-triyl triacetate 
• 572-09-8 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide 
• 106-44-5 p-cresol 
• 604-69-3 β-D-glucose pentaacetate 
• 14581-78-3 4-methylphenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 
• 1010838-90-0 (-)-(2R,3S)-1-(4-β-D-glucopyranosyloxybenzyl)-4-{4-[β-D-glucopyranosyl-(1->6)-β-D-glucopyranosyloxy]benzyl}-2-isobutyltartrate 
• 1010838-91-1 (-)-(2R,3S)-1-(4-β-D-glucopyranosyloxybenzyl)-4-methyl-2-isobutyltartrate 
• 123-08-0 4-hydroxy-benzaldehyde 
• 2887-07-2 4-formylphenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 
• 6919-96-6 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide 
• 59252-47-0 4-(tetra-O-acetyl-β-D-glucopyranosyloxy)benzyl acetate 
• 50-99-7 D-glucose 
• 604-68-2 α-D-glucopyranose peracetylate 
• 174972-80-6 parishin C 

Downstream Products

• 59252-47-0 4-(tetra-O-acetyl-β-D-glucopyranosyloxy)benzyl acetate 
• 1126638-80-9 C₁₃H₁₇ClO₆ 
• 64291-41-4 (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(4-(hydroxymethyl)phenoxy)-tetrahydro-2H-pyran-3,4,5-triyl triacetate 
• 623-05-2 (4-hydroxyphenyl)methanol 

Relevant articles and documents

Rapid biosynthesis of phenolic glycosides and their derivatives from biomass-derived hydroxycinnamates

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.

Gastrodin refining method

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.

Synthesis method and application of gastrodin semihydrate

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.

Transformation mechanisms of chemical ingredients in steaming process of gastrodia elata blume

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.

Synthesis method of gastrodin

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.

A 4 - hydroxy methyl phenyl - beta - D glucopyranoside synthesis method (by machine translation)

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)

A high-purity, high-stability Gastrodin semi-synthetic method

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.

Gastrodin production process

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

Gastrodin Gastrodin and method for the preparation of intermediates for the synthesis of

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.

Gastrodin suitable for industrial production of the high-efficiency high-yield preparation method

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.