Moschus ketone
Muskone
CAS: 541-91-3;22460-48-6;956-82-1
Molecular Formula: C16H30O
Moschus ketone - Names and Identifiers
| Name | Muskone |
| Synonyms | MUSCONE Muskone Muscone HSDB 1219 FEMA 3434 AI3-38746 DL-MUSCONE Musk Ketone Ketone Musk FEMA No. 3434 Methylexaltone Moschus ketone 3-Methylcyclopentadecanone 3-methyl-cyclopentadecanon 3-METHYL-CYCLOPENTADECANONE 3-methylcyclopentadecan-1-one Cyclopentadecanone, 3-methyl- 5-Methyl-1-cyclopentadecanone 3-Methyl-1-cyclopentadecanone 3-Methylcyclopentadecan-1-one 3-METHYL-1-CYCLOPENTADECANONE 3-Methylcyclopentadecanone, dl- |
| CAS | 541-91-3 22460-48-6 956-82-1 |
| EINECS | 208-795-8 |
| InChI | InChI=1/C16H30O/c1-15-12-10-8-6-4-2-3-5-7-9-11-13-16(17)14-15/h15H,2-14H2,1H3 |
Moschus ketone - Physico-chemical Properties
| Molecular Formula | C16H30O |
| Molar Mass | 238.41 |
| Density | 0.9221 |
| Melting Point | -15°C(lit.) |
| Boling Point | 95°C/0.1mmHg(lit.) |
| Flash Point | 145.3°C |
| JECFA Number | 1402 |
| Water Solubility | 430μg/L at 20℃ |
| Solubility | Insoluble in water, glycol, glycerin, insoluble in ethanol, soluble in benzyl benzoate, animal oil and essential oil. |
| Vapor Presure | 0.041Pa at 25℃ |
| Appearance | Light yellow powdery or flake crystals |
| Color | Colourless |
| Maximum wavelength(λmax) | ['285nm(EtOH)(lit.)'] |
| Merck | 14,6313 |
| Storage Condition | Sealed in dry,Room Temperature |
| Refractive Index | 1.4770 to 1.4810 |
| MDL | MFCD00024271 |
| Physical and Chemical Properties | The active ingredient of the Musk aroma is 3-methylcyclopentadecanone, also known as muscone |
| Use | For drugs, Musk spices, fixatives, etc |
Moschus ketone - Risk and Safety
| RTECS | GY0950000 |
| TSCA | Yes |
Moschus ketone - Reference Information
| FEMA | 3434 | 3-METHYL-1-CYCLOPENTADECANONE |
| LogP | 6.06 at 25℃ |
| NIST chemical information | Information provided by: webbook.nist.gov (external link) |
| EPA chemical information | Information provided by: ofmpub.epa.gov (external link) |
| Background Introduction | Musk is a specialty of China, and "Shennong's Materia Medica" lists it as top grade. Liang Tao Hongjing's "Compendium of Materia Medica", Ming Li Shizhen's "Compendium of Materia Medica" and other works have been recorded. Musk is famous for its internal treatment of stroke, middle qi, middle evil and infantile convulsion, and external treatment of bruises and sores. In the National Pharmacopoeia, musk is needed for 10% Chinese patent medicines, and more than 1/4 of Chinese patent medicines are compatible with musk in Beijing and Shanghai. At present, the Chinese patent medicines made by the medical circles in Beijing and Shanghai using muscone instead of natural musk and other Chinese medicines mainly include Suhexiang Pills, Zixue Powder, Zhou's Huisheng Pill, Niuhuang Qingxin Pills, First Dan, Xihuang Pills, Liushen Pills, etc. These Chinese patent medicines made with muscone instead of natural musk are used to treat coronary heart disease, high fever in children, acute gastroenteritis, bruises, inflammation of the Wugong department, mastitis, lymphatic tuberculosis, tonsillitis, mumps and other diseases. Good curative effect. Muscone is the main functional component of natural musk. It can be used as an important component of spices. It has a strong musk aroma that is heavy, soft and pleasant, and can make the essence have an elegant, moist aroma. It is a rare high-grade fragrance. At the same time, muscone also has some important pharmacological effects of natural musk. The clinical application of muscone began in the 2070s. The Beijing pharmaceutical industry first made muscone alone into aerosols and buccal tablets for clinical use to treat coronary heart disease and relieve angina pectoris. |
| Overview | Muscone, scientific name 3-methylcyclopentanone, naturally produced L-body is a colorless liquid with a strong musk smell. Relative density 0.862. (17/4 ℃), melting point -19 ℃, boiling point 15 ℃(12 × 133.322Pa), refractive index 1.4776(17 ℃). Natural muscone is one of the active ingredients extracted by distillation from dry secretions of musk from Bersxoxskii Fleror or Mo-SchumoschiferusL mature male sachet of deer forest musk deer. The synthesized racemate is white needle-like crystals, insoluble in water, soluble in ethanol. In 1906 Walavm found that natural musk contained about 2%. In 1926, the Ruzicka determined that the structure was 3-methylcyclopentanone. The preparation method is to use the complex of dodecatriene nickel to first react with alladiene to become a new complex with three carbon atoms added, and then react it with tertiary butyl isonitrile to form a fifteen-member ring of imine, which is hydrolyzed and reduced to obtain racemic muscone with a yield of 40%. Muscone has the effects of aromatic resuscitation, dredging meridians and collaterals, reducing swelling and relieving pain. Small doses have an excitatory effect on the central nervous system, and large doses have an inhibitory effect. It has excitatory effect on isolated frog heart, androgen-like effect and anti-inflammatory effect. Clinically used for coronary heart disease, angina pectoris, vascular headache, sciatica, vitiligo, etc. This product has been synthesized and produced in China. The pharmacological effects of artificial synthetic products are similar to natural muscone after testing. |
| properties | white or colorless and matte crystal, colorless viscous liquid after melting; It has sweet and soft musk aroma and is extremely durable and strong. Melting point 33 ℃, boiling point 130 ℃/66.6Pa,115~119 ℃/40Pa, relative density d4170.9214; Refractive index nD171.4809; optical rotation rate -3~10.6 (synthetic product is racemic); Soluble in ethanol and oil, almost insoluble in water. |
| pharmacological effects | muscone has the effects of aromatic resuscitation, dredging meridians and activating collaterals, reducing swelling and relieving pain. Small doses have an excitatory effect on the central nervous system, while large doses have an inhibitory effect. It has excitatory effect on isolated frog heart, androgen-like effect and anti-inflammatory effect. Clinically used for coronary heart disease, angina pectoris, vascular headache, sciatica, vitiligo, etc. This product has been synthesized and produced in China. The pharmacological effects of artificial products are similar to natural muscone after testing. Multiple oral administration (5 mg/kg) in rats can significantly shorten the sleep time caused by pentobarbital sodium. The principle is that muscone has the effect of stimulating liver microsomal drug invertase, thus causing rapid destruction and inactivation of pentobarbital sodium in the liver. Its pharmacological effects are as follows: Anti-dementia Studies have shown that muscone can significantly promote calcium uptake in thoracic aorta of scopolamine-induced dementia model rats, and increase intracellular availability of calcium by promoting calcium influx. To achieve the goal of improving learning and memory . It has a significant effect on Alzheimer's disease caused by intracellular availability of calcium lower than the physiological level; it can increase the serum superoxide dismutase (SOD) activity of aging model mice, and reduce the malondialdehyde in the brain tissue (MAO) Activity; at the same time, it can improve the learning and memory function of dementia mice, and exert its anti-dementia effect by scavenging excess free radicals; inhibit the decomposition of monoamine transmitters in the brain, delays the brain nerve transmitter disorder caused by dementia, improves the function of the central nervous system, and thus has a puzzle effect. Anti-cerebral ischemia muscone has a significant protective effect on neuroblastoma cells from hypoxia, glucose deprivation and reoxygenation, suggesting that muscone may be used in the treatment of acute stroke. It can significantly reduce the volume of cerebral infarction in rats with cerebral ischemia-reperfusion injury and reduce the nerve cell injury involved in cerebral ischemia-reperfusion injury. Anti-inflammatory muscone can inhibit the production of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), cyclooxygenase -2(COX-2), inhibitory nitric oxide synthase (iNOS), nitric oxide (NO), matrix metalloproteinase 13, and can significantly inhibit extracellular signal-regulated kinase (ERK1/2) and c-Jun nitrogen-terminal kinase (JNK) signaling pathways role. Anti-myocardial ischemia Muscone can significantly prolong the survival time of myocardial ischemia model rats caused by coronary artery ligation, increase coronary flow, reduce T wave peak value, creatine kinase (CK) and LDH content, and have obvious effects on myocardial ischemia and angina pectoris. It can increase the content of calcitonin gene-related peptide (CGRP) by reducing the release of plasma endothelin (ET), improve the expression of vascular endothelial growth factor (VEGF) in myocardium, thus improving myocardial ischemia and playing a certain protective role. Anti-tumor Muscone has a higher inhibition rate on mouse Ehrlich ascites tumor and leukocyte respiration than normal mice; it has a destructive effect on isolated animal cancer cells, and has a significant effect on the cell respiration of animal tumor tissues Inhibitory effect; through the effect of aromatic qi, promote blood circulation and remove blood stasis, improve blood hypercoagulability, reduce platelet adhesion and aggregation, improve fibrin content, increase fibrinolysis and blood flow, improve the hypoxic state of tumor cell microenvironment, reduce the expression of HIF-1, and reduce the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor (bFGF), thus playing a role in inhibiting tumor angiogenesis. Effect on the central nervous system Muscone has a certain effect on the conditioned reflex of animals, and changes with the dose. The rats were given 5 mg/kg muscone by gavage, which could significantly shorten the sleep time caused by pentytol sodium, but a large dose (100~500 mg/kg) could prolong the sleep time. Therefore, it is believed that a small dose of muscone has an exciting effect on the central nervous system, and a large amount of muscone can also be inhibited. Anti-early pregnancy and anti-implantation Natural musk has obvious excitatory effects on the isolated uterus of pregnant rats, rabbits or guinea pigs after abortion. It can promote the uterine contractility to gradually increase, the rhythm increases, and the effect on the uterus of rabbits in the late pregnancy is more obvious. Therefore, Chinese medicine has always used musk as a contraindication drug for pregnancy. Synthetic muscone has a similar effect. Daily subcutaneous injection of 20 mg of muscone in mice can cause anti-implantation and anti-early pregnancy effects, and the longer the pregnancy, the stronger the anti-pregnancy effect. In addition, muscone has anticoagulant, anti-inflammatory, antibacterial and anti-ulcer effects. |
| toxicology | toxicity test: mice injected with 72~300 mg/kg liquid medicine intraperitoneally have symptoms such as upper abdominal organ adhesion and liver atrophy after 10 days. When the dose was reduced to 38.8 mg/kg, no obvious symptoms were found. subacute toxicity test: rats were divided into groups and injected 55.56 and 27.78 mg/kg intraperitoneally every day for 20 days. The results showed that the former had certain effects on red blood cells, white blood cells and liver of rats. The clinical daily dosage of 9 mg was a safe amount, which had no obvious damage to liver and kidney function, but allergic reactions occurred. Generally, different degrees of itching occurred after 5~15 min of injection, followed by eyelid edema. There are also those who react after 30~50 min of injection, the reaction time is generally 30~60 min, and some can return to normal after 120 min, but the side effects are few when administered by oral and inhalant. Carcinogenic mutagenic test: Cytochrome P450 enzyme system plays a very important role in the process of metabolic activation of mutagens and carcinogens. It can activate the metabolism of promutagens (procarcinogens) to metabolites with mutagenic and carcinogenic effects. The results confirmed that muscone was able to enhance the genotoxic effect of the promutagen/procarcinogen benzo (a) pyrene by influencing the induced metabolic enzyme (CYP1A). |
| preparation method | muscone synthesis methods mainly include three ring-closing methods, ring expansion method and methyl insertion method. The ring-closing method is the synthesis of muscone by an open-chain compound through an intramolecular closed-loop reaction such as aldol condensation, Dickman condensed alcohol ketone condensation or Hornall-Wadsworth-Emmons alkenylation; the ring-expanding method is to synthesize muscone through three-carbon or two-carbon ring expansion with cyclododecanone or cyclotridone as raw materials; the insertion methyl method uses cyclopentanone as raw material to synthesize muscone by introducing methyl at its β position. Because the initial raw materials of the ring expansion method and the insertion methyl method-macrocyclic ketones (such as cyclododecanone, cyclotridenone, cyclopentanone, etc.) are not easy to obtain, the price is more expensive, and the reagent conditions for the reaction are more harsh. It is restricted in industrial applications, so the ring-closing method is the main means of synthesizing muscone. Route 1: racemic muscone is synthesized by five-step reactions of esterification, ketone alcohol condensation, methanesulfonyl substitution, elimination, and methylation using pentadecanedioic acid as raw material. The process is as follows: Route 2: The intermediate 1(2,15-decanedione) is synthesized from 1,10-dibromodecane and methyl acetoacetate by nucleophilic substitution hydrolysis and decarboxylation, or 1, 9-decadiene and acetone are synthesized by free radical coupling 1, then using TiCl4/Bu3N as raw material, 2 is synthesized by cross aldol condensation reaction, 2 is obtained by dehydration under different reaction conditions, and finally the target product is obtained by catalytic hydrogenation. the process is shown in the figure: route 3:®-Citronella: acid and methyl 10-unenoic acid are used as raw materials, TiCl4/Bu3N is used as catalyst, through cross-Claisen condensation reaction, hydrolysis decarboxylation, ring-closing metathesis reaction, and catalytic hydrogenation synthesis. The reaction is divided into three steps. The yields of each step are 76%, 95% and 74% respectively. The total yield can reach 53%. The starting raw materials are easy to obtain, but the reaction conditions are harsh. The details are as follows: Route 4: using tetradecanediic acid and o-phenylenediamine as raw materials, the dibenzimidazole salt is obtained by cyclization quaternization under normal pressure, and then it is added-hydrolyzed with methyl magnesium iodide to obtain 2,15-decane diketone, and then intramolecular cyclization and hydrogenation to obtain muscone, as follows: |
| Pharmacokinetics | Using deuterium labeling method to trace the metabolic process of muscone in vivo shows that the kinetic process of oral administration of muscone in rat plasma and brain tissue can be described by a two-compartment model. absorption and distribution: muscone can quickly enter the central nervous system through the blood-brain barrier after intragastric administration and intravenous injection in mice. The distribution half-life of a single intravenous injection is 1.4 min, and the absorption half-life of a single intragastric injection is 12.6 min. Description The drug absorbs quickly and exerts its efficacy quickly. metabolism and excretion: the elimination rate constants of muscone in brain tissue and plasma are 0.56h and 0.45h respectively, indicating that muscone is eliminated quickly in brain and plasma (the concentration in brain decreases slightly faster than plasma concentration), therefore, there will be no accumulation of muscone in brain. |
| use | has the effect of dilating coronary artery and increasing coronary blood flow, and has certain curative effect on angina pectoris. Generally, it takes effect within 5 minutes after medication (sublingual administration, aerosol inhalation), and the effect of relieving angina pectoris is slightly similar to nitroglycerin. Muscone is a representative variety of macrocyclic musk. The basic chemical structure of macrocyclic musk is 13-19 acyclic and contains at least one functional group. According to the chemical structure, it can be divided into cyclic esters, cyclic lactones, cyclic oxyketones, cyclic ketolides, etc. Among musk-type synthetic spices, the output of macrocyclic musk accounts for 5%. Muscone has a sweet aroma and can be well blended with various spices. The aroma threshold is extremely low (0.001ppm-0.01ppm), and the fragrance lasts for a long time. It is an extremely effective fixative. In pharmacology, it has the role of barren central nervous system, respiratory center and heart, and promotes the secretion of various ureas in drought. It is an important drug for the treatment of mental errors. It can protect coronary arteries, increase coronary flow, and play a role in promoting blood circulation, detumescence, and pain relief. In addition, there is the role of exciting the uterus and enhancing the contraction of uterine smooth muscle, so pregnant women should not use it. Musk is famous for clearing all orifices, opening meridians, penetrating muscles and bones, internal treatment of stroke, middle qi, middle evil and infantile convulsions, and external treatment of iron injury and sores. The addition of musk to high-level calligraphy and painting is not only clear and elegant, but also has the special effect of making calligraphy and painting unchanged for a long time, not water, and anti-corrosion. used for medicine, musk flavor, fixative, etc. |
| specification | sublingual buccal tablets: 30mg per tablet; Aerosol: 180mg per bottle. |
| usage and dosage | contain under the tongue: 0.5~1 tablet each time; Aerosol inhalation, press the valve 1~3 times each time |
| main reference | [1] Ma Lifeng et al. Research Progress in Pharmacology and Synthesis of Muscone. Hebei Chemical Industry. 2010,33(2):11-14. [2] Ma Shichang Editor-in-Chief. Dictionary of organic compounds. Xi'an: Shaanxi Science and Technology Press. 1988. [3] Editor-in-Chief Wang Daquan. Dictionary of Fine Chemical Industry. Beijing: Chemical Industry Press. 1998. Page 626. [4] Yu Weiping, editor-in-chief Li Shoujun. Dictionary of Common Chinese Medicine Words. Jinan: Shandong Science and Technology Press. 1998. [5] Xu Gewen, editor-in-chief Li Buqing. Technical manual for synthetic spice products. Beijing: China Business Publishing House. 1996. [6] feng qiaoqiao et al. research progress on pharmacological effects of muscone. food and medicine. 2015,17(3):212-214. [7] Li jianmin et al. research progress in synthesis of muscone by Guan ring method. Fine petrochemical industry. 2012,29(2):81-84. |
| production method | muscone has a variety of synthesis methods. the raw materials can be cyclohexanone, butadiene, cyclopentanone, etc. The formula using butadiene as raw material fails to be one of the most promising methods studied at present. Twelve carbon -1,5,9-triene is generated from butadiene trice, then hydrogenated and oxidized to cyclododecanone, and then muscone is obtained by multi-step reaction with a yield of 40%. Muscone is the main ingredient of natural musk, generally containing muscone 1.2%-1.4%. The natural musk is distilled by steam for several days, and the injection body is extracted with ether, and made into ammonia urea, then refined, decomposed, and finally refined by distillation. |
| toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |
Last Update：2024-04-09 19:05:12
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