CN107739398A - A kind of propionating catalpol derivatives and its preparation method and application - Google Patents
A kind of propionating catalpol derivatives and its preparation method and application Download PDFInfo
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- CN107739398A CN107739398A CN201710974075.3A CN201710974075A CN107739398A CN 107739398 A CN107739398 A CN 107739398A CN 201710974075 A CN201710974075 A CN 201710974075A CN 107739398 A CN107739398 A CN 107739398A
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
Abstract
The present invention discloses a kind of propionating catalpol derivatives, is esterified to obtain with propionic andydride by Catalpol, while provide its corresponding preparation method and application.Using propionic andydride and Catalpol esterification occurs for the present invention; generate six hydroxyls of Catalpol all or 1 ~ 5 hydroxylic moiety participates in the esterification products of esterification; namely complete propionating or propionating part catalpol derivatives; such catalpol derivatives has good activity of fighting against senium; the blood-brain barrier permeability of Catalpol is improved, esterification yied is up to 96.71%；Thinking is provided for the binding mode and anti-aging effects Mechanism Study of catalpol derivatives and target point protein, the antiaging agent that more further synthesizing activity is higher, bioavilability is higher provides reference, contributes to the later development of Catalpol.
Description
Technical field
The invention belongs to pharmaceutical chemistry and pharmaceutical technology field, and in particular to a kind of propionating catalpol derivatives and its system
Preparation Method and application.
Background technology
Aging typically refers to human body after it grows and reaches the maturity period, with advancing age, in form, structure
With a series of systemic, many degenerations changes necessarily occurred in terms of physiological function, as atrophoderma, bone loss,
Atherosclerosis, senile dementia etc..With the aggravation of population in the world aging trend, various countries researcher long-lived mechanism,
The all many-sides of epigenetic regulation aging, metabolism and aging etc. achieve obvious progress, the research of antiaging agent into
For the focus in current gerontology field, and Chinese medicine with its it is unique the effect of, occupy what is become more and more important in the research of anti-aging
Status.Such as the main effective active composition of the traditional Chinese medicine glutinous rehmannia in China：(Catalpol causes sub- anxious Zhang Xiuli etc. to D- galactolipins
Influence [J] the China biochemical drug magazine of relative antioxidant enzymatic activity in property mouse aging learning and memory and brain, 2011,32
(2):103-106) research is had shown that, Catalpol has anti-aging effects, Li Mengyu etc., and (Catalpol preventing and treating Alzheimer disease effect is ground
Study carefully progress [J] Inpharms research magazine, 2016,43 (2):199-203) and (the Catalpol protects such as Wang Z
rat pheochromocytoma cells against oxygen and glucose deprivation-induced
Injury [J] .Neurological Research, 2008,30 (1):106112) also research shows, Catalpol is in preventing and treating A Er
The nervous system diseases such as Ci Haimo diseases, Parkinson etc. play the role of important.Catalpol is as a kind of small-molecule drug, water
Dissolubility is higher, easily oral, but (the HPLCP-APCI-MA/MA Method for the Determination of such as Wan GQ
Catalpol in Rat Plasma and Cerebropinal Fluid:Application to an in Vivo
Pharmacolinetic Study [J] .Journal of Pharmaceutical and Biomedical Analysis,
2012,70:337-343) research show, Catalpol it is fat-soluble relatively low, be not easy to pass through blood-brain barrier, be distributed in brain it is not high, this
Constrain clinical practice of the Catalpol as antiaging agent.Therefore, structural modification is carried out to Catalpol, obtains higher blood-brain barrier
Permeability is higher, and the catalpol derivatives with activity of fighting against senium have great importance.
2007, (the Catalpol ameliorates cognition deficits and such as Zhang X L
attenuates oxidative damage in the brain of senescentmice induced by D-
Galactose [J] .Pharmacol Biochem Behav, 2007,88 (1):It is 64-72) small in the Kunming of D- galactolipins induction
Found in mouse Ageing Model, compared with control group, the learning and memory ability for injecting the mouse after Catalpol has obtained significantly carrying
It is high.Further research finds that Catalpol adds the activity of SOD and GSH-Px in mouse brain cortex and hippocampus, reduced
Wherein MDA level, and improve Na+-K+The activity of-ATP enzyme, show Catalpol can improve endogenous anti-oxidative enzyme activity and
The generation for reducing free radical plays the effect of anti-aging.2016, (the Catalpol preserves such as Huang J Z
neural functionand attenuates the pathology of Alzheimer′s disease in mice
[J] .Molecular Medicine Reports, 2016,13 (1):491-496) find in an experiment, Catalpol can be by carrying
Reactive oxygen species relevant enzyme in high mouse Cerebral cortex, model mice cerebral cortex is reduced with concentration such as SOD and GSH-Px activity
Middle oxidative stress, can be by adjusting soluble A β in insulin-degrading enzyme40With A β42Level, so as to suppress the formation of senile plaque expelling.
A series of researchs show that glutathione peroxidase (GSH-Px) and hepatocuprein (SOD) are most Kangshuaining mixtures
Thing plays two important target of its anti-aging curative effect.The basic structure of medicine is kept, only makees one on some function bases
Fixed chemical constitution changes, referred to as modifying for chemical structure.Because method is relatively easy, technique relative maturity, modifying for chemical structure
It is the first choice of medicines structure modification.Esterification derivative is to improve a kind of fat-soluble conventional prodrug design strategy of medicine.Medicine point
Son amount is bigger, and volume is bigger, and diffusion coefficient is smaller, and cross-film permeability is lower, so to select the less acid of molecular weight as far as possible
Acid anhydride performs the derivatization.
The content of the invention
Present invention aims at a kind of propionating catalpol derivatives of offer, while its corresponding preparation method is provided and answered
With another goal of the invention for being the present invention.
Based on above-mentioned purpose, the present invention takes following technical scheme：
A kind of propionating catalpol derivatives, it is esterified to obtain with propionic andydride by Catalpol.
During esterification, esterification occurs for all or part of hydroxyl and the propionic andydride of Catalpol.
Structural formula is when Catalpol whole hydroxyl participates in esterification：
The structural formula that 5 hydroxyls participate in esterifications is：
The structural formula that 4 hydroxyls participate in esterifications is：
The structural formula that 3 hydroxyls participate in esterifications is：
The structural formula that 2 hydroxyls participate in esterifications is：
The structural formula that 1 hydroxyl participates in esterification is：
The preparation method of propionating catalpol derivatives, comprises the following steps：
1) Catalpol is dissolved in organic solvent A, adds propionic andydride, at 30-90 DEG C, reacted 12-48h, be evaporated organic
Solvent orange 2 A, obtain product；The mole dosage ratio of the propionic andydride and Catalpol is (6-12) ︰ 1；
2) product of step 1) is dissolved in organic solvent B, adds alkaline agent, stratification, lower floor's aqueous phase is abandoned, to having
Water removal is mutually dried in machine, is evaporated organic solvent B, column chromatography, is evaporated, filters, obtains catalpol derivatives.
Organic solvent A is pyridine in step 1), and the concentration that Catalpol is dissolved in pyridine is 15-25g/L.
Organic solvent B is ethyl acetate in step 2)；Alkaline agent is saturated sodium carbonate solution.
Organic phase is dried water removal using anhydrous sodium sulfate in step 2)；It is evaporated in step 1) and step 2) and takes
Revolving.
The eluant, eluent used in step 2) during column chromatography for dichloromethane and the mixture of methanol, dichloromethane and methanol
Volumetric usage ratio is 5 ︰ 1.
Catalpol is radix rehmanniae recen natural extracts in step 1), purity 98%.
The application of propionating catalpol derivatives, clinical practice of the catalpol derivatives as antiaging agent.
When 6 hydroxyls of Catalpol all participate in esterification, reaction equation is：
Compared with prior art, the invention has the advantages that：
1) using propionic andydride and Catalpol esterification occurs for the present invention, generates six hydroxyls of Catalpol or 1~5 hydroxyl ginseng
Add the esterification products of esterification, namely complete propionating or partially acylated catalpol derivatives, such catalpol derivatives has good
Good activity of fighting against senium, improves the blood-brain barrier permeability of Catalpol, esterification yied is up to 96.71%；For catalpol derivatives with
The binding mode and anti-aging effects Mechanism Study of target point protein provide thinking, and more further synthesizing activity is higher, raw
The higher antiaging agent of thing availability provides reference, contributes to the later development of Catalpol；
2) pyridine not only acts as the effect of solvent, also acts the effect of acid binding agent so that synthesis catalpol derivatives process
It is maintained at suitable acidity medium.
Brief description of the drawings
Fig. 1 is small molecule and the amino acid residue Interactions Mode figure of GSH-Px albumen；
Fig. 2 is small molecule and the amino acid residue Interactions Mode figure of SOD albumen；
Fig. 3 is the HRMS figures of complete propionating catalpol derivatives；
Fig. 4 is complete propionating catalpol derivatives1H NMR scheme；
Fig. 5 is complete propionating catalpol derivatives13C NMR scheme.
Embodiment
Reagent and instrument in following embodiments
Catalpol used in experiment is that laboratory is extracted from glutinous rehmannia, purity 98%；It is propionic andydride, pyridine, sodium acid carbonate, anhydrous
Sodium sulphate is that pure level product is analyzed in the production of Shanghai Alpha Chemical Co., Ltd.；Methanol, acetonitrile are α Cygni friend's fine chemicals
The chromatogram pure level reagent of Co., Ltd's production；Methyl-silicone oil produces for Changzhou Long Cheng organosilicons Co., Ltd；Water is used in chromatogram
Ultra-pure water.
High performance liquid chromatograph used in experiment is the e2695 chromatographs of Waters productions, and mass spectrum used is Thermo companies
The high resolution mass spectrometer of production；RE-2000B types rotary evaporator, DLSB-5/20 type low temperature colds used in Exactive experiments
But liquid circulating pump, the type vavuum pumps of SHB- III, KPCJ-1 type digital-display magnetic stirrers are Zhengzhou Kai Peng laboratory apparatus Co., Ltd
Production；AR224CN type electronic balance (precision 0.0001g) Ao Haosi instrument companies produce；KQ-500DE type numerical control supersonics are clear
Instrument is washed to produce for Kunshan Shu Mei companies；The liquid-transfering gun of 10-100,20-200,100-1000 μ L specifications is German Ai Bende
Eppendorf companies produce；The type ultra-pure water instrument of MiLL-QAdvantage A 10 produces for MiLLipore companies of the U.S.；2XZ-
2 (120L) type vavuum pumps produce for Shanghai Five Dragons vavuum pump factory.
Experimental method
1. high performance liquid chromatograph detection method:Detector, PDA (diode array scanning), 210nm；Chromatographic column,
Agilent-C18,1250 × 4.6mm, 5um.Column temperature, 25 DEG C；Detection method:Take a little sample methanol dissolving sample introduction, sample introduction
Measure as 5 μ L.Mobile phase ratio：Acetonitrile (70)：Water (30).
2. high resolution mass spectrometer testing conditions：ESI ionization sources；Mobile phase is mixed using 10% methanol with high purity water；
Flow velocity is 200 μ L/min；250 DEG C of capillary temperature；Capillary voltage 60V；Tube voltages 120V；The μ L of sample size 10；Aid in gas
For nitrogen (10L/min)；Sheath gas 40L/min；Skimmer voltages 22V；Sweep time 2min；Scanning range：m/z 360-800.
275 DEG C of electric transmission pipe temperature；Scan mode uses positive ion mode.
Embodiment 1
A kind of propionating catalpol derivatives, it is esterified to obtain with propionic andydride by Catalpol.During esterification, 6 hydroxyls of Catalpol or 1
~5 hydroxyls participate in esterification.
The preparation method of propionating catalpol derivatives, comprises the following steps：
1) 100mg (0.27mmol) Catalpol is dissolved in 5mL pyridines, adds 424.57 μ L (3.25mmol) propionic andydrides,
At 60 DEG C, 48h is reacted, liquid phase monitoring reaction terminates, and it is 96.71% to enter Mass Spectrometer Method to obtain esterification yied, is evaporated pyridine, obtains
Product；
2) product of step 1) is dissolved in 40mL ethyl acetate, then adds 40mL saturated sodium carbonate solutions, stood
Layering, lower floor's aqueous phase (adding saturated sodium carbonate solution, stratification, abandon lower floor's aqueous phase, this step is repeated 3 times) is abandoned, uses nothing
Aqueous sodium persulfate organic phase is dried water removal, is evaporated ethyl acetate, column chromatography, is evaporated eluant, eluent, filters removal solvent, obtains
121.27mg catalpol derivatives (0.17mmol, yield 64.35%), the pillar used during column chromatography is silicagel column, eluant, eluent
For dichloromethane and the mixture of methanol, the volumetric usage ratio of dichloromethane and methanol is 5 ︰ 1.
It is evaporated in step 1) and step 2) and takes revolving.
The application of propionating catalpol derivatives, clinical practice of the catalpol derivatives as antiaging agent.
Embodiment 2
A kind of propionating catalpol derivatives, it is esterified to obtain with propionic andydride by Catalpol.During esterification, the part of hydroxyl ginseng of Catalpol
Add esterification.
The preparation method of propionating catalpol derivatives, comprises the following steps：
1) 0.27mmol Catalpols are dissolved in 6.5mL pyridines, add 1.63mmol propionic andydrides, at 30 DEG C, reaction
24h, pyridine is evaporated, obtains product；
2) product of step 1) is dissolved in 30mL ethyl acetate, addition 20mL saturated sodium carbonate solutions, stratification,
Lower floor's aqueous phase (adding saturated sodium carbonate solution, stratification, abandon lower floor's aqueous phase, this step is repeated 3 times) is abandoned, uses anhydrous sulphur
Sour sodium organic phase is dried water removal, is evaporated ethyl acetate, column chromatography, is evaporated eluant, eluent, filters removal solvent, obtains Catalpol
Derivative, the pillar used during column chromatography is the mixture that silicagel column, eluant, eluent are dichloromethane and methanol, dichloromethane and first
The volumetric usage ratio of alcohol is 5 ︰ 1.
Other are the same as embodiment 1.
Embodiment 3
A kind of propionating catalpol derivatives, it is esterified to obtain with propionic andydride by Catalpol.During esterification, the part of hydroxyl ginseng of Catalpol
Add esterification.
The preparation method of propionating catalpol derivatives, comprises the following steps：
1) 0.27mmol Catalpols are dissolved in 4mL pyridines, add 2.43mmol propionic andydrides, at 90 DEG C, react 12h,
Pyridine is evaporated, obtains product；
2) product of step 1) is dissolved in 40mL ethyl acetate, addition 40mL saturated sodium carbonate solutions, stratification,
Lower floor's aqueous phase (adding saturated sodium carbonate solution, stratification, abandon lower floor's aqueous phase, this step is repeated 3 times) is abandoned, uses anhydrous sulphur
Sour sodium organic phase is dried water removal, is evaporated ethyl acetate, column chromatography, is evaporated eluant, eluent, filters removal solvent, obtains Catalpol
Derivative, the pillar used during column chromatography is the mixture that silicagel column, eluant, eluent are dichloromethane and methanol, dichloromethane and first
The volumetric usage ratio of alcohol is 5 ︰ 1.
Other are the same as embodiment 1.
The molecular docking simulated test of embodiment 4
4.1 docking calculation
Using the softwares of Chemoffice 2010 carry out the structure of the propionating catalpol derivatives of smaller ligand and preserve into
MOL2 forms.Small molecule is imported in SYBYL softwares, names and carries out energy-optimised.In optimization process, loading
Gasteiger- H ü ckel electric charges, the structural energy optimization of 1000 steps is carried out to it using the Tripos field of forces.Using Powell
Energy gradient method, the condition of convergence areThe lowest energy conformation of small molecule is obtained, with MOL2 lattice
Formula preserves, and (parameter being related in docking operation is that SYBYL writes from memory in addition to it should be particularly mentioned that to the molecular docking as next step
Recognize)；GSH-Px and SOD albumen files are derived from Protein Data Bank (Http://www.rcsb.org/), utilize Sybyl softwares
The crystallization water and smaller ligand all in albumin crystal are removed, and carries out the pretreatment such as additive polarity hydrogen and power-up lotus.Using
Multi-Channel Surface patterns, generate several active pockets and select a best active pocket of docking effect (logical
Docking experiment is crossed to obtain), threshold values is set to 0.50, and the coefficient of expansion is set to 1, is used as docking with one archetypal molecule of generation；Using height
Accuracy modes are docked, and are given a mark using the uniformity score function of ligand-receptor affinity.
By docking, complete propionating catalpol derivatives (6 hydroxyls of Catalpol participate in esterification) and part are propionating
Catalpol derivatives 2 hydroxyls of Catalpol (participate in esterification) it is right with two kinds of protein (being respectively GSH-Px and SOD) respectively
Connect, docking Score Lists are as shown in table 1, and the corresponding small molecule and amino acid residue phase of complete propionating catalpol derivatives
Interaction ideograph,【With reference to shown in effect Fig. 1 and 2 in other documentary evidences, rod-like molecule is amino acid residue in figure, overstriking
Mallet shape molecule is complete propionating catalpol derivatives；Red represents O atom, and white represents C atoms, and blueness represents N atoms,
Cyanic colours represent H atom】.The dotted line of fluorescent yellow is the hydrogen bond that compound is formed with surrounding amino acid residue.
Table 1 complete propionating (a) and the catalpol derivatives of 2 hydroxyls participation esterifications (b) dock with two kinds of albumen
Point
Wherein：In table 1, Total Score represent total marking, illustrate the combination degree of part and acceptor, with part-
The negative logarithm (- logKd) of the Dissociation equilibrium constant of acceptor is related, and in general score value is bigger, illustrates small molecule and ligand binding
Must be more stable.Crash discloses some unsuitable collisions in binding site, and negative represents infiltration, and score more levels off to zero,
It is better with reference to effect to show；Polar represents the polarity between protein and part, and numerical value is bigger to represent polar interaction to right
The contribution function of binding fruit is bigger.D_Score is to the charge effect between protein acceptor and smaller ligand and Van der Waals work
Evaluation firmly, numerical value are more low better.PMF_Score, i.e. Potential of Mean Force, represent protein ligands source
It is more low better from the Hull nurse time free energy of Thermodynamic parameters, numerical value.G_Score is to hydrogen between smaller ligand and acceptor
Key effect can rotate the evaluation of energy with key, and numerical value is more low better；Chemscore is measure protein receptor and smaller ligand
Rotational energy level, hydrogen bond size etc., its numerical value are the smaller the better.
As shown in Table 1, complete propionating and 2 hydroxyls participate in pair of the catalpol derivatives and GSH-Px and SOD of esterification
It is respectively 8.30,7.15 and 6.47,6.10 to connect total score, and the complete propionating and propionating catalpol derivatives in part of this explanation have
Good activity of fighting against senium, hydroxyl is substituted number has a certain degree of influence to its activity of fighting against senium.
By being learnt in Fig. 1 and Fig. 2, (1) in complete propionating catalpol derivatives and GSH-Px docking scheme, compound with
Surrounding amino acid forms 7 hydrogen bonds.Wherein, No. 4 positions, the carbonylic oxygen atom on No. 10 positions respectively with asparagine (ASN77),
Hydrogen atom on glutamine (GLN78) produces hydrogen bond, the carbonylic oxygen atom on No. 8 positions simultaneously with glycine (GLY80) and group
Hydrogen atom on propylhomoserin (HIS81) produces hydrogen bond.Epoxy radicals and the ehter bond oxygen atom on No. 8 positions with threonine (THR149)
Hydrogen atom form hydrogen bond, No. 6 carbon connect the hydrogen atom formation hydrogen bond on ehter bond oxygen atom and asparagine (ASN77).Ehter bond
Hydrophobic effect is produced with amino acid, carbonyl produces electrostatic interaction and hydrophilic interaction with surrounding amino acid；(2) complete propionating
In catalpol derivatives and SOD docking scheme, compound and surrounding amino acid form 4 hydrogen bonds, wherein, No. 1 position of compound, No. 2
Position, the carbonylic oxygen atom on No. 8 positions respectively with alanine (ALA55), glutamine (GLN48), valine (VAL191)
Hydrogen atom forms hydrogen bond, and the ehter bond oxygen atom on No. 4 positions forms hydrogen bond with the hydrogen atom on glutamine (GLN48).This table
Bright, the avtive spots of complete propionating catalpol derivatives and two receptor proteins is by Hydrogen bonding forces, hydrophobic effect, quiet
Electro ultrafiltration and hydrophilic interaction generate stronger interaction.
The structural characterization of the complete propionating catalpol derivatives of embodiment 5
The present invention utilizes HRMS using complete propionating catalpol derivatives made from the method for embodiment 1,1H NMR and13C
NMR characterizes to it, and spectrogram is respectively as shown in Fig. 4, Fig. 5, Fig. 3.
Target product is computed obtaining M/Z=698.28.
From the figure 3, it may be seen that in the case where responding strong NL=1.50E8, there are 3 main peaks.Its detailed data is exported from mass spectrogram,
According to mass spectrum cation scanning theory, can obtain：M/Z=699.2864 peaks are M+H peaks, M/Z=716.3131 M+NH4 +
Peak, M/Z=721.2773 M+Na+Peak.Measured data is consistent with gross data.
The present invention carries out structural modification using propionic andydride to Catalpol, and complete propionating catalpol derivatives have been made.Molecule pair
Binding fruit shows：The catalpol derivatives and glutathione peroxidase (GSH-Px) and superoxides qi of full propiono protection
The target point protein for changing enzyme (SOD) the two antiaging agents passes through Hydrogen bonding forces, hydrophobic effect, electrostatic interaction and hydrophilic work
With stronger adhesion is generated, it imply that object may have good activity of fighting against senium；The esterification of the Catalpol of synthesis is spread out
Biology, the blood-brain barrier permeability of Catalpol is improved, esterification yied is up to 96.71%；This research is catalpol derivatives and target spot
The binding mode and anti-aging effects Mechanism Study of albumen provide thinking, and more further synthesizing activity is higher, biological profit
The higher antiaging agent of expenditure provides reference, contributes to the later development of Catalpol.
Claims (9)
1. a kind of propionating catalpol derivatives, it is characterised in that be esterified to obtain with propionic andydride by Catalpol.
2. propionating catalpol derivatives as claimed in claim 1, it is characterised in that during esterification, all or part of Catalpol
With propionic andydride esterification occurs for hydroxyl.
3. the preparation method of the propionating catalpol derivatives described in claim 1, it is characterised in that comprise the following steps：
1）Catalpol is dissolved in organic solvent A, adds propionic andydride, at 30-90 DEG C, 12-48 h is reacted, is evaporated organic solvent
A, obtain product；The mole dosage ratio of the propionic andydride and Catalpol is（6-12）︰ 1；
2）By step 1）Product be dissolved in organic solvent B, add alkaline agent, stratification, lower floor's aqueous phase is abandoned, to organic phase
Water removal is dried, is evaporated organic solvent B, column chromatography, is evaporated, filters, obtain catalpol derivatives.
4. the preparation method of propionating catalpol derivatives as claimed in claim 3, it is characterised in that step 1）In it is organic molten
Agent A is pyridine, and the concentration that Catalpol is dissolved in pyridine is 15-25 g/L.
5. the preparation method of propionating catalpol derivatives as claimed in claim 3, it is characterised in that step 2）In it is organic molten
Agent B is ethyl acetate；Alkaline agent is saturated sodium carbonate solution.
6. the preparation method of propionating catalpol derivatives as claimed in claim 3, it is characterised in that step 2）It is middle to use nothing
Aqueous sodium persulfate organic phase is dried water removal；Step 1）With step 2）In be evaporated and take revolving.
7. the preparation method of propionating catalpol derivatives as claimed in claim 3, it is characterised in that step 2）Middle column chromatography
Shi Caiyong eluant, eluent is the mixture of dichloromethane and methanol, and the volumetric usage ratio of dichloromethane and methanol is 5 ︰ 1.
8. the preparation method of propionating catalpol derivatives as claimed in claim 3, it is characterised in that step 1）Middle Catalpol is
Radix Rehmanniae extract, purity 98%.
9. the application of the propionating catalpol derivatives described in claim 1, it is characterised in that the catalpol derivatives are as anti-ageing
The clinical practice of old medicine.
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| CN113817003A (en) * | 2021-10-27 | 2021-12-21 | 浙江爱索拓科技有限公司 | Radioactive isotope tritium labeled catalpol and synthetic method thereof |
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| CN108912183A (en) * | 2018-07-06 | 2018-11-30 | 河南中医药大学 | A kind of catalpol derivatives and its preparation method and application that crotons are acylated |
| CN108912183B (en) * | 2018-07-06 | 2020-09-18 | 河南中医药大学 | Catalpol derivative acylated with croton and preparation method and application thereof |
| CN113817003A (en) * | 2021-10-27 | 2021-12-21 | 浙江爱索拓科技有限公司 | Radioactive isotope tritium labeled catalpol and synthetic method thereof |
| CN113817003B (en) * | 2021-10-27 | 2023-11-24 | 浙江爱索拓标记医药科技有限公司 | Radioisotope tritium-labeled catalpol and synthesis method thereof |
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