Shikimic acid
3,4,5-trihydroxy-1-cyclohexen-1-carboxylic acid
English Name: shikimic acid
3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid; shikimic acid; 97%; (3R, 4S, 5R) - 3,4,5-trihydroxycyclohex-1-enecarboxylic acid; (-) - shikimic acid; kava kava extract
CAS NO. 138-59-0
Chemical formula: 3,4,5-trihydroxy-1-cyclohexen-1-carboxylic acid
Molecular formula c7h10o5
Molecular weight 174.15 [2]
Numbering system editor
CAS No.: 138-59-0
MDL No.: mfcd00066278
EINECS No.: 205-334-2
RTECS No.: gw4600000
BRN No.: 4782717 [2]
Editing of physical property data
1. Character: colorless or white acicular crystal.
2. Solubility: 18% in water at 20 ℃, slightly soluble in ethanol and ether, almost insoluble in chloroform and benzene.
3. Boiling point (OC): 400.5
4. Melting point (OC): 185 ~ 187
5. Flash point (OC): 210.1
6. Relative density (d204): 1.725 [2]
Toxicology data editing
Acute toxicity data:
LD: 1 mg / kg
Oncogenic data:
Oral tdlo: 4000 mg / kg in mice
Tdlo: 400mg / kg
Mutagenicity data:
Dominant intraperitoneal lethal test in mice: 1000mg / kg
Oral dominant lethal test in mice: 3200mg / kg
Morphological transformation test of hamster kidney: 250 mg / L [2]
Molecular structure data editing
1. Molar refractive index: 38.14
2. Molar volume: 100.9
3. Isotonic specific volume (90.2k): 331.7
4. Surface tension (3.0 dyne / cm): 116.6
5. Polarizability: 15.12 [2]
Data editing of computational chemistry
1. Reference value of hydrophobic parameter calculation (xlogp): - 1.7
2. The number of hydrogen bond donors: 4
3. Number of hydrogen bond receptors: 5
4. Number of rotatable chemical bonds: 1
5. Number of tautomers:
6. Topological molecular polar surface area (TPSA): 98
7. Number of heavy atoms: 12
8. Surface charge: 0
9. Complexity: 222
10. Number of isotope atoms: 0
11. To determine the number of atomic structural centers: 3
12. Number of indeterminate atomic stereocenters: 0
13. Determine the number of chemical bond stereocenters: 0
14. Number of indeterminate chemical bond stereocenters: 0
15. Number of covalent bond units: 1 [2]
Property and stability editing
1. Hygroscopic. Can sublimate
2. It exists in tobacco leaves. [3]
Storage method editor
It should be filled with argon and sealed in a cool and dry place. [3]
Synthesis method editing
Shikimic acid is a monomer compound extracted from Illicium verum. [3]
Purpose editor
Shikimic acid can affect arachidonic acid metabolism, inhibit platelet aggregation, inhibit arteriovenous thrombosis and cerebral thrombosis, and has anti-inflammatory and analgesic effects. It can also be used as an intermediate of antiviral and anticancer drugs. This product is often used as pharmaceutical intermediates and has certain irritation, so it is not suitable for direct use.
Organic synthesis. [3]
Shikimic acid has been found for the first time to have obvious antithrombotic effect, which can inhibit immobilization, venous thrombosis and cerebral thrombosis. In order to elucidate its antithrombotic mechanism, researchers studied the effects of shikimic acid on platelet aggregation and coagulation, and analyzed the relationship between its mechanism of action and arachidonic acid metabolism. The results suggest that shikimic acid may play an antithrombotic role by affecting arachidonic acid metabolism, inhibiting platelet aggregation and coagulation system. Huang Jianmei, an associate professor of Beijing University of traditional Chinese medicine, is an expert in the study of Illicium. Facing the reporter's interview, Huang Jianmei said that shikimic acid is a very common thing. If it wasn't for avian influenza, if it wasn't for shikimic acid extracted from Illicium verum by Roche company, who would never pay attention to shikimic acid, no one would be aware of Illicium verum It is also a traditional Chinese medicine. [2]
Biosynthesis editor
Phosphoenolpyruvate (PEP) produced by glycolysis interacts with d-erythritose-4-phosphate produced by pentose phosphate pathway to form intermediate 3-deoxy-d-arabinoheptanoic acid-7-phosphate, which is further cyclized to shikimic acid. Shikimic acid reacts with pep to form 3-enolpyruvate shikimic acid-5-phosphate, then Pi is removed to form branched acid. Cladistic acid is an important key substance in shikimic acid pathway. Its subsequent fate can be divided into two branches: one is to tryptophan, the other is to form prephenic acid first, then to arogenicacid, and then to form phenylalanine, and the other is to form tyrosine (Fig. 5-7). The reason why glyphosate, a broad-spectrum herbicide, can control weeds is that it can inhibit the enzyme that catalyzes the synthesis of 3-enolpyruvate shikimate-5-phosphate from shikimic acid and PEP. This pathway exists in higher plants, fungi and bacteria, but not in animals, so animals can not synthesize phenylalanine, tyrosine and tryptophan, which must be supplemented from food. [4]
Future editor
Shikimic acid has two development prospects in academic circles
Antibacterial and antitumor
In 1987, it was reported that Japanese scholars found that a compound of shikimic acid had obvious inhibitory effect on HeLa cells and Ehrlich ascites carcinoma, and could prolong the survival time of mice inoculated with leukemia cell L1210, and the toxicity was relatively low. It was pointed out that the inhibitory effect was mainly due to the interaction between shikimic acid compound and thiohydrides Reaction. The other compound had no antagonistic effect on leukemia cell line L1210, but had certain antagonistic effect on Trichophyton Trichophyton atcc9972. In 1988, sun kuailin and others in China carried out preliminary in vitro antibacterial and antitumor experiments on a shikimic acid derivative. It was proved that this compound had inhibitory effect on leukemia cell L1210 in vitro similar to that of dimycin. [4]
cardiovascular system
Sun Jianning, from Beijing University of traditional Chinese medicine, studied the effects of shikimic acid and its derivatives, triacetylshikimic acid and isopropylidene shikimic acid, on cardiovascular system. They found that the three compounds all had the effects of antithrombotic and inhibiting platelet aggregation, and studied their mechanism of action.
Shikimic acid pathway is an important metabolic pathway in plants, fungi and microorganisms, which has seven enzymatic processes. Dehydroquinic acid (DHQ) and shikimate dehydrogenase (SDH) promote the third and fourth stages of shikimate pathway. In most microorganisms, DHQ and SDH are monofunctional, but in plants, DHQ and SDH can fuse to form enzymes with two functions. The advantage of dhq-sdh bifunctional enzyme is to increase the efficiency of metabolic pathway by limiting the mass of intermediate in competitive pathway. Christendat's team at the University of Toronto recently analyzed the dhq-sdh structure of Arabidopsis thaliana. The researchers completed the co crystallization of dhq-sdh enzyme and shikimic acid for the first time by gas-phase suspension method, and then added nicotinamide adenine dinucleotide phosphate (NADP +) to the crystal to form a triple complex. The formation of dehydrogenated shikimic acid product at DHQ site indicates that SDH shikimic acid NADP (H) is an active complex for shikimic acid oxidation, and there are active sites in the concave structure of dhq-sdh. Dhq-sdh protein can distinguish the metabolites in shikimic acid pathway by face-to-face localization, and increase the transfer efficiency of metabolites from DHQ to SDH domain. This model has been confirmed by the available kinetic data, and it is believed that SDH plays a role in storing metabolites in shikimic acid pathway. [4]
