67-97-0 Usage
Uses
Used in Pharmaceutical Industry:
Vitamin D3 is used as a vitamin medicine for the treatment of rickets and osteomalacia. It promotes intestinal absorption and deposition of calcium and phosphorus.
Used in Food and Health Products Industry:
Vitamin D3 is used as an additive in the production of food, health products, and other related products. It can maintain normal metabolism of calcium and phosphorus, promoting the body's absorption of these minerals.
Used in Animal Feed Industry:
Vitamin D3 is used as a feed additive to maintain normal metabolism of calcium and phosphorus in animals, such as pigs and poultry. It helps prevent rickets and other bone-related issues in animals.
Used in Rodenticide:
Vitamin D3 is used in bait for vermin control as a rodenticide. It is a steroid hormone that regulates body levels of calcium and phosphorus and is involved in bone mineralization.
Used in Respiratory Disease Treatment:
Vitamin D3 is under investigation as a selective phosphodiesterase-4 inhibitor (PDE-4 inhibitor) for treating respiratory diseases involving chronic inflammation, such as asthma or COPD (smoker's lung).
Used as a Carnitine Replenisher:
Vitamin D3 is used as a carnitine replenisher in the treatment of peripheral arterial disease.
Used as a Vitamin D3 Analogue:
Vitamin D3 is used as an analogue in various applications, including the modulation of the proliferation and differentiation of both normal and cancer cells, and having antiproliferative and antimetastatic effects on breast, colon, and prostate cancer cells.
Used in Food Fortification:
Vitamin D3 is used to strengthen margarine, dairy products, infant food, milk, milk drinks, solid drinks, and ice cream. It helps maintain calcium absorption and homeostasis.
Used in Agricultural Applications:
Vitamin D3 is used for the control of rats and mice in agricultural applications. It is not approved for use in EU countries but is registered for use in the U.S. and other countries.
Vitamin D
Vitamin D is steroid derivatives. It is the general term for the compounds that have similar structures and have the effect of normal skeletal growth and maintenance. At present, there are at least more than ten kinds of sterols that have vitamin D activity. But there are only two important matters, which are known as pro-vitamin D. One is ergosterol that exists in vegetable oil or yeast, which can generate vitamin D2 when irradiated by sunlight or ultraviolet radiation. It is also known as cholecalciferol or ergocalciferol. Another is 7-dehydrochlesterol that exists in the skin. It will become vitamin D3 after irradiated by the light. It is also called cholecalciferol. D2 and D3 have similar structures. They are B ring derivatives of precursors of the sterol. The difference is that the side chain of vitamin D2 has a methyl group and one double bond.
Vitamin D2 and D3 are all colorless crystals. The melting point of D2 and D3 respectively are 115~118℃ and 84~85℃. They are insoluble in water, and soluble in ethanol and other organic solvents. Their solubility in vegetable oil are small. Crystalline vitamin D should be stored in dark to light and oxygen at low temperature. Vitamin D3 is more stable than D2. It is not easy to be oxidized. Vitamin D has heat stability in the near neutral solution. It will be rapidly destroyed in the acidic solution, and the rate of destruction depends on strength and temperature of the acid. However, it is stable in alkaline solution. It can tolerate alkali treatment even under high temperature conditions.
In the industrial synthesis products, vitamin D3 is more. Vitamin D3 is sensitive to light and can be damaged by minerals and oxidation. But vitamin D3 has good stability after esterification and coated by gelatin, sugar and starch. The activity of vitamin D3 is also represented by International Units (IU). The amount of IU crystals vitamin D3 is 0.025μg. The active ingredient content of the industrial synthesis of vitamin D3 additive is more of 500,000 IU/g or 200 000 IU/g. For vitamin additives products, there are also additives that contain vitamin A and vitamin D3. The activity is usually 1g additive containing 500,000 IU of vitamin A and 100,000 IU of vitamin D3. The two has no antagonistic effect. And their production and use are very convenient. Vitamin D can increase the absorption and metabolism of calcium and phosphorus, prevent swine rickets, and promote the development of teeth and bones. Vitamin D dosage of pig feed is 125~200IU/kg. The amount for piglets is higher than growing pig. The amount of boar and growing pig are similar.
Physiological function
Under UV irradiation vegetative ergosterol and animal 7-dehydrogenation are absorbed and convert into vitamin D2 and vitamin D3. The two vitamin D must produc further chemical changes before used by the body. 7-dehydrocholesterol first form into 25-hydroxy derivative in the liver, then generate active ingredient 1,25-dihydroxyvitamin cholecalciferol [1,25 (OH) 2D5] by hydroxylation. The main function of vitamin D is to promote intestinal absorption of calcium and phosphorus, and regulate metabolism of calcium and phosphorus in order to maintain the body's calcium and phosphorus balance. Calcium absorbed from intestinal canal can be transported through the blood circulation from the liver and kidneys to the bone and other calcified tissues, and excret from the bone to the kidneys. This transport mechanism is controlled by vitamin D. When the concentration of calcium, phosphorus in the body decreases, vitamin D can dissociate calcium from the bone. In addition, vitamin D can also control kidney tubules to reabsorb calcium and phosphorus.
Vitamin D2 and vitamin D3 has the same function on ammals cows and pigs. But vitamin D3 for poultry (birds) is ten times stronger activity than vitamin D2.
Vitamin D deficiency can reduce the intestinal absorption of calcium, and cause the decomposition of bone calcium and phosphorus. Young livestock will appear osteomalacia. Adult animals are easy to appear osteoporosis. Vitamin D deficiency can also lead to animal sternum and spine deformation and layers laying soft-shell eggs. Because vitamin D controls the absorption of calcium and phosphorus, too much vitamin D in dietary can cause hypercalcemia, make excess calcium deposit in the heart, blood vessels, joints, pericardium or intestinal wall, and finally lead to heart failure, joint stiffness or bowel Road disorders.
Sunbathing is the most economical source of vitamin D. ergosterol or 7-dehydrogenation cholesterol in the feed will turn into vitamin D by ultraviolet radiation inside an animal for the utilization of carcass. Hay, corn leaves yeast, barley, oats, wheat after insolation and yeast after ultraviolet treatment are better sources of vitamin D. Animal products can be directly provide vitamin D to livestock, such as eggs, milk. The content of vitamin D in cod liver oil is very high. Diets need to be added vitamin D for reared animals and insufficient sunlight animal.
The above information is edited by the lookchem of Ge Qian.
Content analysis
Same with “vitamin D2 (01043)”. But all ergocalciferol is replaced by cholecalciferol.
Toxicity
LD50 oral in rat: 42mg/kg
Maximum level
GB 14880-94: same with “01043, vitamin D2”
FDA, §18. 1950(2000): same with “01043, vitamin D2”
Chemical property
White columnar crystals or crystalline powder, odorless and tasteless. Melting point 84~88℃, specific rotation αD20 =+105°~+112°. Easily soluble in chloroform, soluble in alcohol, ether, cyclohexane and acetone, slightly soluble in vegetable oil, insoluble in water. Good heat resistance, but unstable for light. Easily oxidized in air. Rats by oral LD1042mg/kg.
Production method
1. 7-dehydrocholesterol is dissolved in ethanol, and then treated with ultraviolet light to open the ring. The reaction mixture is concentrated, frozen and filtered. The filtrate is concentrated under reduced pressure nitrogen to dryness to give a crude liquid vitamin D3. Then it is refined to get vitamin D3.
2. Vitamin D3 naturally exists in the liver, egg yolk and milk. The production method in the industry starts from vegetable oil or yeast to extract 7-dehydrocholesterol that is not absorbed by the human body. Then it is dissolved in chloroform or cyclohexane. And then it converts to vitamin D3 by the ultraviolet radiation in the quartz glass flask.
3. Vitamin D3 naturally exists in the liver, egg yolk and milk. The production method in the industry starts from vegetable oil or yeast to extract 7-dehydrocholesterol that is not absorbed by the human body. Then it is dissolved in chloroform or cyclohexane. And then it converts to vitamin D3 by the ultraviolet radiation in the quartz glass flask.
Originator
Vitamin D, Country Life
Indications
Vitamin D is the collective term for a group of compounds
formed by the action of ultraviolet irradiation on
sterols. Cholecalciferol (vitamin D3) and calciferol (vitamin
D2) are formed by irradiation of the provitamins 7-
dehydrocholesterol and ergosterol, respectively. The
conversion to vitamin D3 occurs in the skin. The liver is
the principal storage site for vitamin D, and it is here that
the vitamin is hydroxylated to form 25-hydroxyvitamin
D. Additional hydroxylation to form 1,25-dihydroxyvitamin
D occurs in the kidney in response to the need for
calcium and phosphate
Indications
Vitamin D3, through its active metabolite, 1,25-
(OH)2D3, also plays an important role in maintaining
calcium homeostasis by enhancing intestinal calcium
absorption, PTH-induced mobilization of calcium from
bone, and calcium reabsorption in the kidney.
Manufacturing Process
5 g of 7-dehydrocholesteryl acetate (prepared by W.R. Ness, R. S. Kostic and
Mosetting, J. Am. Chem. Soc. 78, 436, 1956) were dissolved in 500 ml of nhexane. This solution was irradiated with ultraviolet ray by recyclicly passing it
through a quartz apparatus surrounding 450 w high pressure mercury vapor
lamps for 80 minutes. After irradiation and then the distillating off of nhexane the solution was added with 50 ml of ethanol and the ethanolic
solution was left to stand overnight at the temperature of -20°C. The formed
crystals were filtered off from ethanolic solution and filtrate was heated at the
temperature 78°C for 4 hours. After cooling of filtrate, the cooled filtrate was
added with 4 ml of ethanolic solution containing 0.7 g of potassium hydroxide
to effect a reaction at the temperature of 20°C and under nitrogen for 60
minutes. The reaction product was added with 0.7 ml glacial acetic acid and
then ethanol was distilled off under reduced pressure from the reaction
product. The obtained residue was extracted with 50 ml of n-hexane and
extract was washed with water and n-hexane was distilled off from extract to
obtain 2.5 g of yellow oily matter containing vitamin D3. The content of
vitamin D3 in yellow oily matter was 40.2% by weight.
Therapeutic Function
Vitamin, Antirachitic
Biosynthesis
The primary supply of vitamin D3 in humans is not obtained
from the diet but rather is derived from the ultraviolet
photoconversion of 7-dehydrocholesterol to vitamin
D3 in skin. Thus, vitamin D3 synthesis varies with the seasons.
D3 is a prohormone and requires further metabolic
conversion to exert biological activity in its target organs. The liver and the kidney are the major sites
of metabolic activation of this endogenous sterol hormone.
The initial transformation of D3 occurs in the liver
and is catalyzed by the enzyme 25-OH-D3-hydroxylase
to form 25-(OH)D3; this is the primary circulating form
of D3. Circulating 25-(OH)D3 is then converted by the
kidney to the most active form of D3, 1,25-(OH)2D3, by
the 1-(OH)-D3-hydroxylase enzyme. Blood concentrations
of 1,25-(OH)2D3 are approximately one fivehundredth
of those of 25-(OH)D3. 1, 25-(OH)2D3 is converted
to the metabolite 24R,25-(OH)2D3, which is capable
of suppressing parathyroid secretion.
In addition to the endogenous metabolites, some exogenous
sterols possess biological activity similar to
that of D3. Ergocalciferol (vitamin D2) is derived from
the plant sterol ergosterol and may act as a substrate for
both the 25-hydroxylase and the 1-hydroxylase enzyme
systems of the liver and kidney to form 25-(OH)D2 and
1,25-(OH)2 D2, respectively. Ergocalciferol (vitamin D2)
is the form used in commercial vitamins and supplemented
dairy products. Dihydrotachysterol, another
sterol that is used as a therapeutic agent, also functions
as a substrate for the hydroxylase enzymes in the liver
and kidney.
Health Hazard
SYMPTOMS: Symptoms of exposure to Vitamin D3 may include weakness, fatigue, lassitude headache, nausea, vomiting, diarrhea, polyuria, polydipsia, nocturia, decrease urinary concentrating ability, proteinuria, tissue calcification, hypertension and osteoporosis.
Fire Hazard
Flash point data for Vitamin D3 are not available. Vitamin D3 is probably combustible.
Trade name
DELSTEROL?; DEPARAL?; D3-
VIGANTOL?; QUINTOX?; RAMPAGE?; RICKETON?;
TRIVITAN?; VIGORSAN?; VITINC DAN-DEE-3?
Biochem/physiol Actions
Vitamin D acts through a receptor that is a member of the ligand-dependent transcription factor superfamily. Modulates the proliferation and differentiation of both normal and cancer cells. Has antiproliferative and antimetastatic effects on breast, colon, and prostate cancer cells. Activated vitamin D receptors in intestine and bone maintain calcium absorbance and homeostasis.
Mechanism of action
1, 25-(OH)2D3 exerts its influence within target tissues
through high-affinity sterol-specific intracellular receptor
proteins.The D3 receptor, similar to steroid receptor
systems, translocates the hormone from the cell cytoplasm
to the nucleus, where biological response is initiated
via transcription and translation.
Clinical Use
The principal disorder associated with inadequate
vitamin D intake is rickets. The low blood calcium and
phosphate levels that occur during vitamin D deficiency
stimulate parathyroid hormone secretion to restore calcium
levels. In children, this deficiency
leads to the formation of soft bones that become deformed
easily; in adults, osteomalacia results from the
removal of calcium from the bone.Vitamin D deficiency
may occur in patients with metabolic disorders, such as
hypoparathyroidism and renal osteodystrophy. The requirement
for vitamin D is slightly higher in members
of darker-pigmented races, since melanin interferes
with the irradiation that produces vitamin D3 in the
skin. People with limited exposure to the sun may need
to supplement vitamin D intake.
Side effects
The hypercalcemia resulting from hypervitaminosis
D is responsible for toxic symptoms such as muscle
weakness, bone pain, anorexia, ectopic calcification, hypertension,
and cardiac arrhythmias. Toxicity in infants
can result in mental and physical retardation, renal failure,
and death.
Safety Profile
Poison by ingestion. An
experimental teratogen. When heated to
decomposition it emits acrid smoke and
irritating fumes.
Potential Exposure
Sterol rodenticide used in bait for vermin control. Vitamin D is a steroid hormone that has an important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. Not approved for use in EU countries
Drug interactions
Potentially hazardous interactions with other drugs
Antiepileptics: the effects of vitamin D may
be reduced in patients taking barbiturates or
anticonvulsants.
Diuretics: increased risk of hypercalcaemia with
thiazides.
Sevelamer: absorption may be impaired by sevelamer.
Metabolic pathway
Cholecalciferol (vitamin D3) is the mammalian form of vitamin D. It is
normally produced in the skin by the action of UV light on its precursor, 7-
dehydrocholesterol. Essential amounts of the vitamin are obtained thus or
from dietary sources such as fish oils. The active form of the vitamin is
1,25-dihydroxy-cholecalciferol. Its formation occurs in two stages: 25-
hydroxylation in the liver, followed by 1-hydroxylation in the kidney (see
Engstrom and Koszewski, 1989 and references cited therein).
Metabolism
Within the liver, cholecalciferol is hydroxylated to
calcidiol (25-hydroxycholecalciferol) by the enzyme
25-hydroxylase. Within the kidney, calcidiol serves as
a substrate for 1-alpha-hydroxylase, yielding calcitriol
(1,25-dihydroxycholecalciferol), the biologically active
form of vitamin D3.Cholecalciferol and its metabolites are excreted mainly in
the bile and faeces.
Purification Methods
It is converted into its 3,5-dinitrobenzoyl ester and crystallised repeatedly from acetone. The ester is then saponified and the free vitamin is isolated. [Laughland & Phillips Anal Chem 28 817 1956, Beilstein 6 III 2811, 6 IV 4149.]
Degradation
It is unstable in light and air and in acidic media.
It is inactivated within a few days under normal exposure conditions. This
is due to oxidation and fragmentation of the triene functionality.
Toxicity evaluation
Another steroidal rodenticide is
cholecalciferol, which is in fact the naturally occurring
vitamin D3. This compound is an essential factor for
vertebrates but in large doses causes hypercalcemia,
resulting in calcification and degeneration of various
soft tissues, ultimately leading to death. In baits,
cholecalciferol may be combined with other, usually
anticoagulant, rodenticides. The main natural source of
cholecalciferol is fish liver oil, but it is manufactured from
ergosterol.
Incompatibilities
Sensitive to air, light, and moisture. Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.
Waste Disposal
Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material’s impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.
Check Digit Verification of cas no
The CAS Registry Mumber 67-97-0 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 7 respectively; the second part has 2 digits, 9 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 67-97:
(4*6)+(3*7)+(2*9)+(1*7)=70
70 % 10 = 0
So 67-97-0 is a valid CAS Registry Number.
InChI:InChI=1/C27H44O/c1-19(2)8-6-9-21(4)25-15-16-26-22(10-7-17-27(25,26)5)12-13-23-18-24(28)14-11-20(23)3/h12-13,19,21,24-26,28H,3,6-11,14-18H2,1-2,4-5H3/b22-12+,23-13-
67-97-0Relevant articles and documents
Microflow High-p,T Intensification of Vitamin D3 Synthesis Using an Ultraviolet Lamp
Escribà-Gelonch, Marc,No?l, Timothy,Hessel, Volker
, p. 147 - 155 (2018)
Herewith a new process concept for synthesis is presented which combines both UV-photoirradiation and high-p,T intensification (photo-high-p,T) in continuous flow. The application of this procedure to Vitamin D3 synthesis promotes thermal shifting of the equilibrium from the reaction intermediate to the product. This is enabled by microreactors which allow operation under harsh conditions such as the high temperature used here. This provides, to our best knowledge, a new kind of process combination (novel process window). As a result, in less than 1 min, 42% conversion of 7-dehydrocholesterol can be achieved giving a 17% yield and 40% selectivity of Vitamin D3. This approach enhances productivity by up to 2 orders of magnitude compared with the current capillary based vitamin D3 synthesis, because, under the microflow conditions, photochemistry can be performed at fairly high concentration and up to 20 times faster.
Photochemical transformations of 7-dehydrocholesterol
Grigoryan,Martiryan,Nersesyan,Markaryan
, p. 509 - 511 (2009)
Photochemical transformations of 7-dehydrocholesterol were performed with a two-lamp experimental circulation installation equipped with a ferrioxalate actinometer and were monitored by UV spectroscopy and high-performance liquid chromatography. The quant
Preparation method of vitamin D3
-
, (2022/03/27)
The invention provides a preparation method of vitamin D3, which comprises the following steps: by taking a compound A as a substrate, sequentially carrying out photochemical reaction, thermal isomerization reaction, crystallization and hydrolysis reaction to obtain the vitamin D3, wherein the compound A has a structure as shown in a formula I in the specification, Rb is one of Rb and Ra is an electron donating group; the illumination condition is ultraviolet irradiation. When the method is used for preparing the vitamin D3, the high-purity vitamin D3 crystal can be prepared without column chromatography, and the method is suitable for large-scale production, high in yield and strong in controllability.
Novel industrial method for preparing vitamin D3 by taking stigmasterol as raw material
-
Paragraph 0010; 0054; 0055, (2021/05/05)
The invention provides a novel industrial method for preparing vitamin D3 by taking stigmasterol as a raw material. The method comprises the following steps: sequentially carrying out hydroxyl acetylation, side chain oxidation, side chain isopentane reduction and hydrogenation on stigmasterol to obtain cholesterol acetate, and then sequentially carrying out oxidation, hydrazone formation, hydrazone removal, hydrolysis, illumination and the like to obtain the vitamin D3. The invention provides a novel method for preparing vitamin D3 from stigmasterol, and the method has the advantages of mild reaction conditions and high yield, and is suitable for industrial production.
Vitamin D3 purification method
-
Paragraph 0030; 0031; 0032-0034, (2021/03/13)
The invention discloses a vitamin D3 purification method which comprises the following steps: a1, mixing organic amine, a first organic solvent, vitamin D3 oil and aryl chloride to react, and then adding water to stop the reaction; a2, washing the product obtained in the step a1 with water, performing drying and filtering, carrying out reduced pressure distillation, performing dissolving, carryingout secondary reduced pressure distillation, carrying out cooling and crystallizing; b1, dissolving vitamin D3 methyl benzoate in methanol, and dropwise adding a strong alkaline solution to perform reacting; b2, carrying out reduced pressure distillation on the substance obtained in the step b1, then carrying out liquid separation, washing an organic phase with water, and carrying out drying, filtering, carrying out secondary reduced pressure distillation, dissolving, cooling and recrystallizing; c1, dissolving the vitamin D3 crude product in a third organic solvent, and then performing stirring for decolorization; and c2, filtering the product obtained in the step c1, carrying out reduced pressure distillation on the filtrate, and carrying out dissolving, cooling, recrystallizing, filtering, and drying to obtain the vitamin D3. The vitamin D3 purified by the purification method disclosed by the invention has the advantages of higher purity, lower harmful impurity content and higher stability.
IMPROVED PHOTOCHEMICAL SYNTHESIS OF VITAMIN D3 USING SENSITIZERS
-
Page/Page column 16-17; 19-27, (2020/12/01)
The present invention discloses an improved photochemical synthesis of vitamin D3 from 7-dehydrocholesterol alone or in combination with sterol precursors in presence of the photosensitizer of Formula I in high yield and with reduced levels of impurities.
IRRADIATION PROCESS OF PRO VITAMIN D
-
Page/Page column 11; 12; 16, (2020/11/30)
The invention discloses an improved process for production of vitamin D3 from 7- dehydrocholesterol (7- DHC) and to a simple process for recovery unreacted 7-DHC for further reuse. The invention further describes a process for isolation and purification of Vitamin D3.
New industrial method for producing vitamin D3 by taking wool fat as raw material
-
Paragraph 0047; 0048, (2019/06/13)
The invention provides a new industrial method for producing vitamin D3 by taking wool fat as a raw material. The new industrial method comprises the following steps: carrying out saponification and primary purification on the wool fat in a low alcohol solution, thus obtaining a cholesterol crude product; directly carrying out acetylation on the cholesterol crude product, thus obtaining high-purity cholesterol acetate; then sequentially carrying out oxidizing, hydrazone forming, hydrazone removing, hydrolyzing, illuminating and the like, thus obtaining the vitamin D3. A production technology disclosed by the invention is efficient, green and environment-friendly, is high in product yield and is suitable for industrial production, and the manufacturing cost of the vitamin D3 is greatly reduced; a saponification technology is ingenious in filtrate treatment, has no generation of waste liquid and waste and is more beneficial for environment protection.
Synthesis method of vitamin D3 analogue
-
Paragraph 0033-0037, (2019/08/30)
The invention discloses a synthesis method of a vitamin D3 analogue. The invention discloses a photochemical reaction method of preparing a cis-intermediate (I) from a trans-initiator (II). The prepared intermediate can be used as an intermediate for the synthesis of active vitamin D analogy such as alfacalcidol, calcitriol, and the like. The synthesis conditions of the active substances become mild, the side reactions are reduced, and the yield is increased.
Syntheses of 7-dehydrocholesterol peroxides and their improved anticancer activity and selectivity over ergosterol peroxide
Tian, Na-Na,Li, Chao,Tian, Na,Zhou, Qian-Xiong,Hou, Yuan-Jun,Zhang, Bao-Wen,Wang, Xue-Song
, p. 14843 - 14846 (2017/12/15)
7-Dehydrocholesterol peroxide (5α,8α-epidioxycholest-6-ene-3β-ol, CEP) and its acetate and hemisuccinate derivatives were synthesized and isolated for the first time, which exhibit improved anticancer activity and selectivity over ergosterol peroxide (5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol, EEP), showing potential as new chemotherapeutic agents.
