Capsaicin

Base Information

• Chemical Name: Capsaicin
• CAS No.: 404-86-4
• Deprecated CAS: 912457-62-6
• Molecular Formula: C18H27NO3
• Molecular Weight: 305.417
• Hs Code.: 29399990
• European Community (EC) Number: 206-969-8
• NSC Number: 757844,56353
• UNII: S07O44R1ZM
• DSSTox Substance ID: DTXSID9020241
• Nikkaji Number: J1.529F,J29.362H
• Wikipedia: Capsaicin
• Wikidata: Q273169
• NCI Thesaurus Code: C339
• RXCUI: 1992
• Pharos Ligand ID: JAL94J53FRK2
• Metabolomics Workbench ID: 38086
• ChEMBL ID: CHEMBL294199
• Mol file: 404-86-4.mol

Synonyms:Styptysat;6-Nonenamide, 8-methyl-N-vanillyl-, (E)- (8CI);8-Methyl-N-vanillyl-6-nonenamide, (E)-;6-Nonenamide, N-[ (4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-, (E)-;trans-8-Methyl-N-vanillyl-6-nonenamide;6-Nonenamide,N-[(4-hydroxy-3-methoxyphenyl) methyl]-8-methyl-,(6E)-;Capsaicin (JAN/USP);N-[(4-hydroxy-3-methoxy-phenyl)methyl]-8-methyl-non-6-enamide;(E)-N-[(4-hydroxy-3-methoxy-phenyl)methyl]-8-methyl-non-6-enamide;(E)-N-((4-Hydroxy-3-methoxyphenyl)-methyl)-8-methyl-6-nonenamide;Zostrix;Capsaicin [USAN];6-Nonenamide, 8-methyl-N-vanillyl-, (E)-;6-Nonenamide, N-((4-hydroxy-3-methoxyphenyl)methyl)-8-methyl-, (6E)-;Prestwick_204;Capsaicin [in oleoresin of capsicum];EPA Pesticide Chemical Code 070701;6-Nonenamide, N-((4-hydroxy-3-methoxyphenyl)methyl)-8-methyl-, (E)-;FEMA No. 3404;Zostrix (TN);Ratden PE 40;N-((4-Hydroxy-3-methoxyphenyl)methyl)-8-methyl-6-nonenamide, (E)-;N-(4-Hydroxy-3-methoxybenzyl)-8-methylnon-trans-6-enamide;(E)-8-Methyl-N-vanillyl-6-nonenamide;

Chemical Property of Capsaicin

Chemical Property:

• Appearance/Colour: Off-white crystalline solid
• Melting Point: 62-65 °C(lit.)
• Refractive Index: 1.5100 (estimate)
• Boiling Point: 511.5 °C at 760 mmHg
• PKA: 9.76±0.20(Predicted)
• Flash Point: 263.1 °C
• PSA: 58.56000
• Density: 1.041 g/cm³
• LogP: 4.18050
• Storage Temp.: 2-8°C
• Solubility.: H2O: insoluble
• Water Solubility.: insoluble
• XLogP3: 3.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 9
• Exact Mass: 305.19909372
• Heavy Atom Count: 22
• Complexity: 341

Purity/Quality:

Capsaicin 99%, ^*data from raw suppliers

trans-Capsaicin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T, T+
• Hazard Codes: T,T+
• Statements: 25-37/38-41-42/43-36/37/38
• Safety Statements: 22-26-28-36/39-45-36/37/39

MSDS Files:

SDS file from LookChem

Useful:

• Chemical Classes: Biological Agents -> Plant Toxins
• Canonical SMILES: CC(C)C=CCCCCC(=O)NCC1=CC(=C(C=C1)O)OC
• Isomeric SMILES: CC(C)/C=C/CCCCC(=O)NCC1=CC(=C(C=C1)O)OC
• Recent ClinicalTrials: Capsaicin 179 mg Patch Versus Oral Duloxetine in Patients With Chemotherapy-induced Peripheral Neuropathy
• Recent EU Clinical Trials: An interventional, Phase III, double-blind, randomized, controlled, parallel-group, multi-site, clinical trial evaluating the efficacy and safety of Qutenza? in subjects with post-surgical neuropathic pain
• Recent NIPH Clinical Trials: The influence of experimental pain on swallowing function
• Description: Capsaicin is the main chemical that makes chili peppers hot. Capsaicin is an animal repellent that is also used against insects and mites. Capsaicin was first registered for use in the United States in 1962. The U.S. Environmental Protection Agency considers it to be a biochemical pesticide because it is a naturally occurring substance. The chemical compound capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue it comes in contact with. Capsaicin and several related compounds are called capsaicinoids and are produced as a secondary metabolite by chili peppers, probably as deterrents against herbivores. Pure capsaicin is a hydrophobic, colorless, odorless, crystalline to waxy compound. Capsaicin is a terpene alkaloid that has been found in Capsicum and has diverse biological activities. It induces inward currents in HEK293 cells expressing rat transient receptor potential vanilloid 1 (TRPV1; EC50 = 0.64 μM at neutral pH), an effect that can be blocked by the TRPV1 inhibitor A-425619. Capsaicin (10 and 50 μM) decreases LPS-induced prostaglandin E2 (PGE2; ) production, as well as reduces LPS- and IFN-induced nitric oxide (NO) release in isolated mouse peritoneal macrophages. Capsaicin induces substance P release in rat spinal cord slices with an EC50 value of 2.3 μM. It reduces acetylcholine- or phenylquinone-induced writhing (ED50s = 1.33 and 1.38 mg/kg, respectively, s.c.) but has no effect on the latency to paw withdrawal in the hot plate test in mice (ED50 = >20 mg/kg, s.c.). Formulations containing capsaicin have been used in the treatment of nerve pain associated with shingles. Capsaicin has a mild, warm-herbaceous odor and a burning pungent taste (at 10 ppm). It is used in compounded flavors for sauces where the pungent note is desired. This substance is present in several species of Capsicum (Family, Solanaceae). The sensation of pain, accompanied by irritation and inflammation, is due to substance P depletion from sensory (afferent) nerve fibers. These properties are used to study the physiology of pain and the effects as a counterirritant and gastrointestinal stimulant. This substance may be prepared from 3-chloro-2-isopropyltetrahydropyran; biosynthesis from Capsicum frutescens; separation form cis-capsaicin, pelargonic acid vanilamide, and dihydrocapsaicin, reaction of capsaicin.
• Uses: Capsaicin is what makes chili peppers hot. It is an irritant.for mam- mals, but not for birds. This may be because birds spread the seeds better than mammals. It causes a burning sensation in any mam- malian tissue with which it comes in contact. Capsaicin is a nonpolar molecule; it dissolves in fats and oils, not in water. This is why water does not take away the burning sensation, but whole milk or other fat-containing liquids or foods will. As an ingredient in medicines, capsaicin is used to relieve pain from arthritis, muscle aches, and sprains. It is a rubefacient, meaning it dilates blood vessels. The heat effect overwhelms nerves, causing a localized numbing sensation. Capsaicin is also used in pepper spray. A representative lot is a 5:1 E:Z mixture. It is used as a tool in neurobiological research. Prototype vanilloid receptor agonist. Topical analgesic. K channel blocker; multiple sclerosis therapy analgesic (topical), depletes Substance P, neurotoxic Capsaicin analogue (C175680). It is used as a tool in neurobiological research. Prototype vanilloid receptor agonist. Topical analgesic. Capsaicin is used in many topical ointments used to relieve the pain of peripheral neuropathy (treatment of pain in the nerve endings near the surface of the skin). As a tool in neurobiological research.
• Physical properties: Appearance: crystalline white powder, with highly volatile and pungent odor. Solubility: freely soluble in alcohol, ether, benzene, and chloroform; slightly soluble in carbon disulfide, petroleum, and hydrochloric acid; insoluble in water. Melting point: 65?°C.
• Indications: Capsaicin (Zostrix) is approved for the relief of pain following herpes zoster infection (postherpetic neuralgia). The drug depletes neurons of substance P, an endogenous neuropeptide that may mediate cutaneous pain. It is applied to affected skin after open lesions have healed. Local irritation is common.
• Clinical Use: In clinical practice, capsaicin is mainly used for topical administration, such as in the treatment of osteoarthritis and rheumatoid arthritis pain, diabetic nerve pain, pain after surgery, chemotherapy- or radiotherapy-induced oral pain, psoriasis, etc. Capsaicin irritates the mucous membrane to cause sneezing, nose bleeding, coughing, mucus secretion, tears, bronchoconstriction, breathing difficulties, and other symptoms. The main adverse effects of capsaicin preparations are contact dermatitis, skin inflammation or blisters, and in severe situation burn-like lesion.

Technology Process of Capsaicin

There total 32 articles about Capsaicin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 91.0%

Vanillylamin (1196-92-5) + (E)-8-Methylnon-6-enoic acid chloride (95636-02-5) → capsaicin (404-86-4,912457-62-6)

Guidance literature:

Vanillylamin; With sodium hydrogencarbonate; In chloroform; water; at 20 ℃; for 0.75h;

(E)-8-Methylnon-6-enoic acid chloride; In chloroform; water; at 20 - 40 ℃; for 1h;

DOI:10.1002/adsc.201301148

Reference yield: 75.0%

trans-8-methyl-6-nonenoic acid (59320-77-3) + vanillylamine hydrochloride (7149-10-2) → capsaicin (404-86-4,912457-62-6)

Guidance literature:

With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; In N,N-dimethyl-formamide; at 20 ℃; for 2h; Schlenk technique;

DOI:10.1016/j.tet.2018.08.049

Reference yield:

trans-8-methyl-6-nonenoic acid (59320-77-3) → capsaicin (404-86-4,912457-62-6)

Guidance literature:

With thionyl chloride; Behandeln des Reaktionsprodukts mit 4-Aminomethyl-2-methoxy-phenol in Aether;

upstream raw materials:

trans-8-methyl-6-nonenoic acid

Vanillylamin

(E)-8-Methylnon-6-enoic acid chloride

(E)-N-[(4β-D-glucopyranosyloxy)-3-methoxyphenylmethyl]-8-methylnon-6-enamide

Downstream raw materials:

(E)-[8-[bis(tert-butoxycarbonylmethyl)aminomethyl]-6-bromo-7-hydroxycoumarin-4-yl]methyl 2-methoxy-4-[(8-methylnon-6-enamido)methyl]phenyl carbonate

Refernces

• 1、 Hamada, Hiroki,Ono, Tsubasa,Shimoda, Kei. "Regioselective hydroxylation and dehydrogenation of capsaicin and dihydrocapsaicin by cultured cells of Phytolacca americana". . p. 103 - 107. Retrieved 2022/03/18.
• 2、 Anderson, Mattias,Afewerki, Samson,Berglund, Per,Cordova, Armando. "Total synthesis of capsaicin analogues from lignin-derived compounds by combined heterogeneous metal, organocatalytic and enzymatic cascades in one pot". . p. 2113 - 2118. Retrieved 2014/07/07.