73-31-4 Usage
description
Melatonin is a hormone secreted by the pineal gland, and its chemical structure was 5-methoxy-N-acetyl tryptamine, the physiological function of inhibiting gonad, thyroid, adrenal gland, parathyroid gland and pituitary function, inhibit precocious puberty, reduce pituitary Melanotropin secretion; and has a central nervous system function, can improve the convulsion the threshold, cause drowsiness. When pinealectomy after the animal experiment showed hyperplasia of the glands, weight increase, especially sex and sexual organs of immature rats early, pituitary secretion of LH and FSH increased, increasing secretion of thyroid and adrenal cortex hormone melatonin. More reduced pituitary MSH and whiten the skin of this role. Effects on the central nervous system, in the human EEG showed slow rhythm, increased seizure threshold, sleepiness, but does not affect their behavior and personality, of temporal lobe epilepsy and Ba Jinsen disease can reduce the motor nerve Abnormal EEG changes.
Chemical properties
Melatonin is a slightly off-white, odourless crystalline powder. It is very slightly soluble in water and in dilute hydrochloric acid.
Melatonin is a small molecule, a derivative of the amino acid tryptophan, N-acetyl-5 methoxytryptamine. It is a potent hormone with well-recognized activities and the potential to influence many bodily functions. It is produced by the pineal gland in the brain and is secreted when the body recognizes darkness. Melatonin has intense effects on the timing of the sleep/awake cycle, regulating the circadian rhythms of several biological functions. This is its most studied biological activity. Melatonin, as a multifunctional hormone, appears to regulate or modulate other functions in humans through the activation of its receptors and works as a strong antioxidant that protects the DNA. Melatonin’s antioxidant activity may reduce Parkinson’s disease development, prevent cardiac arrhythmia, and, in animals, promote longevity.
Mechanism of action
Melatonin is a naturally occurring hormone produced by the pineal gland and is structurally related to serotonin. Physiologically, melatonin secretion increases soon after the onset of darkness, peaks at 2-4 am and diminishes during the second half of the night. Melatonin is associated with the control of circadian rhythms and entrainment to the light-dark cycle. It is also associated with a hypnotic effect and increased propensity for sleep.
The activity of melatonin at the MT1 MT2 receptors is believed to contribute to its sleep-promoting properties via their distinct actions on the circadian clock. The MT1 receptors are thought to inhibit neuronal firing, while the MT2 receptors have been implicated in the phase-shifting response.
Uses
Different sources of media describe the Uses of 73-31-4 differently. You can refer to the following data:
1. 1. Melatonin can be used as medicine health care products, so as to enhance people’s immune function, preventing aging and back to youth. What’s more, it is also a kind of natural “sleeping pill”.
2. Melatonin is a kind of hormone secreted by pineal body of pituitary gland in the body. The amount of melatonin has something to do with light. The weaker the light is, the more the melatonin is, whereas the less. In addition, it is helpful to one’s sleep.
3. Biochemical research.
2. Melatonine can be used in sleep induction, modifies circadian rhythm, antioxidant, free radical scavenger
3. Immunostimulant;Melatonin receptor ligand
4. Melatonin has complex effects on apoptotic pathways, inhibiting apoptosis in immune cells and neurons but enhancing apoptotic cell death of cancer cells. Inhibits proliferation/metastasis of breast cancer cells by inhibiting estrogen receptor action.
Biological Activity
Different sources of media describe the Biological Activity of 73-31-4 differently. You can refer to the following data:
1. Melatonin is a naturally compound found in animals, plants, and microbes. It is a hormone secreted by the pineal gland. Melatonin can directly neutralize a number of ROS, stimulate several antioxidant enzymes, reduce UV-induced erythema, modulate the expression of apoptosis and alleviate sleep disturbances. The mechanism of biological effects is via activation of melatonin receptors or protection of nuclear and mitochondrial DNA.
In the skin, melatonin scavenges and inactivates free radicals arising from UV irradiation. Melatonin represents a substance which protects cells from UVA and UVB action in vitro and in vivo experiments. Preincubation with melatonin can lead to the normalization of the decreased UV-induced mitochondrial membrane potential. Such effects are followed by suppression of the activation of mitochondrial pathway-related initiator caspase 9 (casp-9), but not of death receptor-dependent casp-8. Melatonin also down-regulates casp-3/casp-7 and reduces PARP activation (Fischer et al,. 2008).
2. Endogenous hormone that acts as an agonist at melatonin receptors MT 1 and MT 2 . Exhibits a prominent role in the control of circadian rhythm, displays immunomodulatory activity and acts as a powerful antioxidant in vivo .
Physiological functions
1. The effect to brain: the melatonin obtained by brain mainly gathers in midbrain and hypothalamus and it adds the activity of brain pyridoxal kinase, thus promoting glutamic acid decarboxylation to γ-amino butyric acid, 5-hydroxytryptophane decarboxylation to 5-hydroxytryptamine, both of which can inhibit the increase of the neurotransmitter content and have an effect of adjustment and mitigation on central nervous system.
2. The effect to hypothalamus and pituitary: materials like polypeptide produced by pineal body still have thyrotropin-releasing hormone(TRH) and luteinizing hormone releasing hormone(LRH) which are same with what hypothalamus produces except AVT. After injection of melatonin, gonadotropin (GnH)(FSH,LH) and melanocyte stimulating hormone(MSH) are lowered while growth hormone increases. Cutting pineal gland will cause pituitary hypertrophy, increase pituitary secretion and lower prolactin(PRL) and antidiuretic hormone (ADH).
3. The relation to gonad: melatonin has an inhibitory effect on the reproductive system. Clinically, main cytoma of pineal body can lead to pubertal delay and when teratoma appears in pineal body, it may result in sexual precocity because main cells are excluded. Ambient light and sympathetic nerve can affect the function of the reproductive system by inhibiting the synthesis and release of melatonin in pineal gland.
4. The relation to thyroid: by injecting melatonin, thyroid secretion will decrease. This may be caused through the inhibition of the hypothalamus release and Thyroid Stimulating Hormone (TSH) secretion of pituitary, hence holding back the function of thyroid.
5. The relation to adrenal cortex: melatonin has a strong inhibitory effect on adrenal cortex. If we inject pineal body extracts to healthy people, we will find that their aldosterone secretion and 17-ketosteroid output will decrease.
6. The relation to pancreatic island: melatonin can lower blood glucose and increase sugar tolerance. In conclusion, pineal gland can assist pituitary to jointly adjust endocrine function and play an vital role in keeping relatively constant in body environment and controlling some endocrine function, especially for gonad.
Synthesis of Melatonin
Pineal cells obtain tryptophan from blood circulation and become 5-hydroxytryptophane catalyzed by hydroxylase and 5-hydroxytryptophane turns into 5-hydroxytryptamine after decarboxylated by decarboxylase. There are three possible changes for 5-hydroxytryptamine: for the first part it may turn into 5-hydroxyl-benzpyrole acetic acid when deaminated by monoamine oxidase; for another part, some 5-hydroxytryptamine will leave the pineal cell and be taken in by sympathetic nerve ending and stored with neurotransmitter and noradrenalin; for the remaining part, the 5-hydroxytryptamine will be acetylated by N-acetyl-5-hydroxy tryptamine transferase and then be o-methoxy by hydroxylation indole-o-methyl converzyme, finally forming melatonin. After being synthesized, melatonin will be released by cells and enter into blood circulation through cerebrospinal fluid or directly, where noradrenalin may strengthen the synthesis, the speed of which depends on activity of hydroxylase in liver microsomes. Catalyzed by the hydroxylase, 6-hydroxylmelatonin is formed, soon afterwards it combines with glucuronic acid and sulfate, excreting through urine.
Description
Melatonin, at times referred to as the “hormone of darkness,” normally is secreted during the night.
It is synthesized in the pineal gland, and its secretion is controlled by the suprachiasmatic nucleus, following an
endogenous circadian rhythm. Studies indicate that melatonin may
Chemical Properties
Off-White Powder
Occurrence
Melatonin is a naturally occurring hormone in the body.
Definition
ChEBI: A member of the class of acetamides that is acetamide in which one of the hydrogens attached to the nitrogen atom is replaced by a 2-(5-methoxy-1H-indol-3-yl)ethyl group. It is a hormone secreted by the pineal gland in humans.
World Health Organization (WHO)
Melatonin is promoted as a cure for travel sickness, jet-lag and
insomnia and has recently been claimed in the United States to reverse the ageing
process. A synthetic version has been freely available from health food shops and
pharmacies as a "nutritional supplement" since 1993.
General Description
A hormone that has been postulated as being a mediator of photic-induced anti-gonadotropic activity in photoperiodic mammals. Counteracts the apoptotic effects of etoposide in bone marrow cells. Melatonin receptors are coupled to a G-protein system. Inhibits rat cerebellar nitric oxide synthase (NOS).
Biochem/physiol Actions
Hormone; mediates photoperiodicity in mammals; inhibits cerebellar nitric oxide synthetase; peroxynitrite scavenger. Melatonin has complex effects on apoptotic pathways, inhibiting apoptosis in immune cells and neurons but enhancing apoptotic cell death of cancer cells. Inhibits proliferation/metastasis of breast cancer cells by inhibiting estrogen receptor action.
Clinical Use
Melatonin is most effective in young individuals and appears to be less effective in elderly individuals (possibly because of a decreased number of receptors). Melatonin causes a phase shift of approximately 1 hour per day. This means that the use of melatonin in the morning can delay the onset of evening sleepiness, whereas melatonin taken in the evening has been associated with faster onset of sleep and increased total sleep time. Melatonin is sold as a food supplement in the United States, but it has become popular for use as a hypnotic and for alleviating jet lag (a flight across five or more time zones) and helping to resynchronize individuals who have difficulty adapting to night-shift work. have effects on circadian rhythm and sleep processes. The presence of a pharmacologically specific receptor for melatonin in which the molecular structure is known are referred to as MT1, MT2, and MT3 receptors. The MT1 and MT2 receptors are high-affinity G protein coupled receptors, whereas MT3 is a form of quinone reductase. The MT1 receptor appears to be primarily involved in initiating sleep, whereas the MT2 receptor appears to mediate melatonins effect in the eye, circadian rhythm, and vascular effects. The importance of MT3, although widely distributed in different tissues, is currently unknown. The normal physiological concentration of melatonin observed at night is approximately 100 to 200 pg/mL, and oral doses of 0.1 to 0.3 mg of melatonin are adequate to obtain these concentrations even though melatonin frequently is given at doses of 1 to 10 mg to obtain supraphysiological levels. These higher doses may be the reason for some of the side effects not currently associated with the melatonin receptors.
Veterinary Drugs and Treatments
Melatonin may be useful to treat Alopecia-X in Nordic breeds, canine
pattern baldness, or canine recurrent flank alopecia in dogs.
It has been used anecdotally for the treatment of sleep cycle disorders
in cats and geriatric dogs and to treat phobias and separation
anxiety in dogs. Melatonin implants are used in the mink and fox
pelt industries to promote the development of luxurious hair coats.
Implants are also used to improve early breeding and ovulation
rates in sheep and goats. Preliminary research is being done for this
purpose in horses also.
In pigs, one study (Bubenik, Ayles et al. 1998) demonstrated that
5 mg/kg in feed reduced the incidence
of gastric ulcers in young
pigs.
Check Digit Verification of cas no
The CAS Registry Mumber 73-31-4 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 3 respectively; the second part has 2 digits, 3 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 73-31:
(4*7)+(3*3)+(2*3)+(1*1)=44
44 % 10 = 4
So 73-31-4 is a valid CAS Registry Number.
InChI:InChI=1/C13H16N2O2/c1-9(16)14-6-5-10-8-15-13-4-3-11(17-2)7-12(10)13/h3-4,7-8,15H,5-6H2,1-2H3,(H,14,16)
73-31-4Relevant articles and documents
Selective hydroformylation of N-allylacetamide in an inverted aqueous two-phase catalytic system, enabling a short synthesis of melatonin
Verspui, Goeran,Elbertse, Guido,Sheldon, Frank A.,Hacking, Michiel A. P. J.,Sheldon, Roger A.
, p. 1363 - 1364 (2000)
Water increases the selectivity in the Rh-phosphine catalysed hydroformylation of N-allylacetamide; an aqueous-organic biphasic system, containing a hydrophobic Rh-catalyst, provided facile catalyst/product separation, after which the aqueous product phase could be used in a one-pot synthesis of N-acetyl-5-methoxytryptamine (melatonin).
Mechanisms of NO release by N1-nitrosomelatonin: Nucleophilic attack versus reducing pathways
De Biase, Pablo M.,Turjanski, Adrian G.,Estrin, Dario A.,Doctorovich, Fabio
, p. 5790 - 5798 (2005)
A new type of physiologically relevant nitrosamines have been recently recognized, the N1-nitrosoindoles. The possible pathways by which N1-nitrosomelatonin (NOMel) can react in physiological environments have been studied. Our results show that NOMel slowly decomposes spontaneously in aqueous solution, generating melatonin as the main organic product (k = (3.7 ± 1.1) × 10-5 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37°C, anaerobic). This rate is accelerated by acidification (kpH 5.8 = (4.5 ± 0.7) × 10-4 s-1, kpH 8.8 = (3.9 ± 0.6) × 10-6 s-1 Tris-HCl (0.2 M) buffer at 37°C), by the presence of O2 (k o = (9.8 ± 0.1) × 10-5 s-1 pH 7.4, 37°C, [NOMel] = 0.1 mM, P(O2) = 1 atm), and by the presence of the spin trap TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl; ko = (2.0 ± 0.1) × 10-4 s-1, pH 7.4, 37°C, [NOMel] = 0.1 mM, [TEMPO] = 9 mM). We also found that NOMel can transnitrosate to L-cysteinate, producing S-nitrosocysteine and melatonin (k = 0.127 ± 0.002 M-1 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37°C). The reaction of NOMel with ascorbic acid as a reducing agent has also been studied. This rapid reaction produces nitric oxide and melatonin. The saturation of the observed rate constant (k = (1.08 ± 0.04) × 10-3 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37°C) at high ascorbic acid concentration (100-fold with respect to NOMel) and the pH independence of this reaction in the pH range 7-9 indicate that the reactive species are ascorbate and melatonyl radical originated from the reversible homolysis of NOMel. Taking into account kinetic and DFT calculation data, a comprehensive mechanism for the denitrosation of NOMel is proposed. On the basis of our kinetics results, we conclude that under physiological conditions NOMel mainly reacts with endogenous reducing agents (such as ascorbic acid), producing nitric oxide and melatonin.
A practical synthesis of N-acetyl-5-methoxy-tryptamine (melatonin)
Hwang, Ki-Jun,Lee, Tae-Suk
, p. 2099 - 2104 (1999)
The pineal hormone melatonin is conveniently prepared in simple one pot operation by treating 4-methoxyphenylhydrazine hydrochloride(6) with acetic anhydride and 4-aminobutyraldehyde dimethylacetal(4) in a mixed solvent system of acetic acid/ethanol/water.
Melatonin- And Ferulic Acid-Based HDAC6 Selective Inhibitors Exhibit Pronounced Immunomodulatory Effects in Vitro and Neuroprotective Effects in a Pharmacological Alzheimer's Disease Mouse Model
He, Feng,Chou, C. James,Scheiner, Matthias,Poeta, Eleonora,Yuan Chen, Natalia,Gunesch, Sandra,Hoffmann, Matthias,Sotriffer, Christoph,Monti, Barbara,Maurice, Tangui,Decker, Michael
, p. 3794 - 3812 (2021)
The structures of melatonin and ferulic acid were merged into tertiary amide-based histone deacetylase 6 (HDAC6) inhibitors to develop multi-target-directed inhibitors for neurodegenerative diseases to incorporate antioxidant effects without losing affinity and selectivity at HDAC6. Structure-activity relationships led to compound 10b as a hybrid molecule showing pronounced and selective inhibition of HDAC6 (IC50 = 30.7 nM, > 25-fold selectivity over other subtypes). This compound shows comparable DPPH radical scavenging ability to ferulic acid, comparable ORAC value to melatonin and comparable Cu2+ chelating ability to EDTA. It also lacks neurotoxicity on HT-22 cells, exhibits a pronounced immunomodulatory effect, and is active in vivo showing significantly higher efficacy in an AD mouse model to prevent both Aβ25-35-induced spatial working and long-term memory dysfunction at lower dose (0.3 mg/kg) compared to positive control HDAC6 inhibitor ACY1215 and an equimolar mixture of the three entities ACY1215, melatonin and ferulic acid, suggesting potentially disease-modifying properties.
Recyclable and reusablen-Bu4NBF4/PEG-400/H2O system for electrochemical C-3 formylation of indoles with Me3N as a carbonyl source
Cheng, Didi,Li, Jingyi,Li, Yujin,Ling, Fei,Liu, Lei,Liu, Tao,Zhong, Weihui
supporting information, p. 4107 - 4113 (2021/06/17)
A safe, practical and eco-friendly electrochemical methodology for the synthesis of 3-formylated indoles has been developed by the utilization of Me3N as a novel formylating reagent. Stoichiometric oxidants, metal catalysts, and activating agents were avoided in this method, and an aqueous biphasic system ofn-Bu4NBF4/PEG-400/H2O was used as a recyclable and reusable reaction medium, which made this electrosynthesis approach more sustainable and environmentally friendly. This process expanded the substrate scope and functional group tolerance for bothN-EDG andN-EWG indoles. Furthermore, late-stage functionalization and total/formal synthesis of drugs and natural products were realized by means of this route.
Preparation method of melatonin
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Paragraph 0049; 0056-0058; 0090-0093, (2020/03/03)
The invention relates to the technical field of chemical synthesis of medicines, in particular to a preparation method of melatonin. The preparation method of the melatonin comprises the following steps: (a) subjecting phthalimide, 1,3-dichloropropane, sodium iodide and ethyl acetoacetate to a reaction in a solvent under the action of alkali to obtain a compound I; (b) performing a ring closing reaction on the compound I and p-methoxyphenyl diazonium salt in the presence of alkali and a solvent to obtain a compound II; (c) hydrolyzing the compound II under an alkaline condition, and carrying out decarboxylating under an acidic condition to obtain a compound III; and (d) carrying out an acetylation reaction on the compound III to obtain melatonin. According to the preparation method, phthalimide, 1,3-dichloropropane, ethyl acetoacetate and the like are used as raw materials, and the price of the raw materials is low; the intermediate compound I can be obtained through a one-step method,so reaction steps and time are shortened; moreover, the conditions of each reaction step are relatively mild, the raw materials are easy to obtain, and high yield can be obtained.
