68-26-8 Usage
Uses
Used in Pharmaceutical Industry:
Vitamin A is used as an intermediate in the production of Atracurium Besilate, a muscle relaxant used during surgery.
Used in Nutritional Supplements:
Vitamin A is used as a nutritional factor to support overall health. It is found in various dietary sources, including liver, milk, butter, cheese, eggs, and fish liver oils, as well as carotenoids from fruits and vegetables. It is stored primarily in the liver in esterified form and transported in the blood by retinol-binding protein (RBP).
Used in Skincare Industry:
Retinol, a form of vitamin A, is used as a skin revitalizer to enhance skin radiance and treat conditions associated with chronological aging, such as wrinkles and fine lines. It is also used to treat dermatological disorders, including acne, follicular and lesion papules, actinic keratosis, oily skin, and rosacea. Retinol is considered necessary for normal epidermal cell growth and differentiation and stimulates the production of new blood vessels in the skin, improving skin tone. It has antioxidant capacities and protects dermal fibers by counteracting the increased activity of enzymes that degrade collagen and elastin when the skin is exposed to UV rays. However, retinol can be drying to the skin when used for a prolonged period of time or in concentrations that are too high.
Used in Food Industry:
Vitamin A is used as a nutrient in various food products, such as liver, fortified margarine, egg, and milk. Vitamin A palmitate can be found in frozen egg substitute. It is stable in the absence of air and does not have an appreciable loss by heating or freezing.
Used in Industrial Production:
Vitamin A1 (retinal) is produced from β-carotene, which can be obtained by fermentation of corn, soybean meal, kerosene, thiamin, and α-ionone. The dry mass after fermentation contains 120 to 150 g product/kg.
Used in Medical Treatment:
Vitamin A is used as a mucolytic, a substance that helps break down and thin mucus in the respiratory system, making it easier to cough up and clear from the airways.
Originator
Acon ,Endo
History
The vitamin research is the great achievement in the development of life sciences,
while human beings only took half a century to discover and understand vitamins.
However, everything is still very difficult for scientists in the early stage of vitamin
discovery. From 1913 to 1915, Elmer McCollum and Marguerite Davis indicated
that the growth rate was maintained by at least two different kinds of growth factors:
one can be separated from eggs or butter, and the other one which multiple neuritis of chicks and pigeons can be extracted by water; thus they were
named fat-soluble vitamin A and water-soluble vitamin B.preventedIn 1919, the researchers demonstrated that fat-soluble vitamin A not only sup ported the rate of growth but also prevented eye dryness and night blindness in the
process of property study. In 1920, Dr. J.C. Drummond named this active lipid as
vitamin A. It exists in cod liver oil and prevents the occurrence of eye dryness and
night blindness.
Indications
Vitamin A, or retinol, is essential for the proper maintenance
of the functional and structural integrity of epithelial
cells, and it plays a major role in epithelial differentiation.
Bone development and growth in children
have also been linked to adequate vitamin A intake.
Vitamin A, when reduced to the aldehyde 11-cis-retinal,
combines with opsin to produce the visual pigment
rhodopsin. This pigment is present in the rods of the
retina and is partly responsible for the process of dark
adaptation.
Manufacturing Process
Manufacturing process for Vitamin A includes these steps as follows: Step A: Synthesis of Preparation of ethyl ether of ethynyl-β-ionol;Step B: Coupling Reaction; Step C:Semi-Hydrogenation of Coupling Product;Step D:Hydrolysis of Semi-Hydrogenated Coupling Product. Separation of Vitamin A from the product obtained was achieved by acetylating the total reaction product using pyridine-acetic anhydride at room
temperature and chromatographing on alumina neutralized with acetic acid. A
fairly clean separation was achieved. The Vitamin A acetate fraction was
sufficiently pure to become crystallized from pentane at -15°C when seeded
with a pure Vitamin A acetate crystal.
When the Vitamin A acetate was converted to the alcohol form of Vitamin A,
the final product showed the characteristic infrared and ultraviolet absorption
curves for Vitamin A. Similar results were obtained using as co-solvents (with
the liquid ammonia) ethylene diamine and ether; pentane; tetrahydrofuran;
diethylamine and hexamethylphosphoramide.
World Health Organization (WHO)
Vitamin A, a fat-soluble vitamin, is used in the treatment and
prevention of vitamin A deficiency resulting from inadequate dietary intake. It has
been demonstrated to be teratogenic at high doses (more than 25,000 IU per day).
Daily dosages of less than 10000 IU seem to be free of this risk. Retinol (vitamin A)
is listed in the WHO Model List of Essential Drugs.
Synthesis Reference(s)
Tetrahedron, 51, p. 2435, 1995 DOI: 10.1016/0040-4020(94)01108-C
Biochem/physiol Actions
Retinol and its derivatives exhibit anti-aging properties. Retinol is used for treating wrinkles and signs of aging. However, due to its photo instability and skin irritation potency, it is hardly used in cosmetic formulations. Retinol is also used as a therapeutic for dermatoses. Its deficiency leads to xerosis and follicular hyperkeratosis.
Pharmacology
Intake of vitamin A precursors, such as carotenoids, retinyl esters, retinol, and reti nal, can maintain the epithelial cell differentiation, normal proliferation, and visual
function. All of these substances can be metabolized into retinol, retinal, and reti noic acid. But unlike retinol and retinal, retinoic acid cannot be reduced to retinol
and retinal. Intake of retinoic acid can only maintain the systemic function of vita min A.Visual and vitamin A. 11-cis-retinal plays an important role as a photographic
group of retinal cones and visual pigments in rod cells. 11-cis-retinal would be
transformed into all-trans-retinal form under the light induction. The dissociation of
all-trans retinal and opsin was coupled with the nerve stimulation of the brain’s
visual center. By a series of biochemical processes, nerve impulses format in the rod
cells at the end of synapse, and then the optic nerve conducts the nerve impulses
along. The visual process is a component renewable cycle, and all-trans-retinal can
be enzymatically modified to 11-cis form in dark conditions.The systemic effects of vitamin A. Vitamin A not only significantly affects visual
function but also has a greater physiological impact than visual function. Vitamin A
deficiency destroys the visual cycle, leads to dark adaptation damage (night blind ness or nyctalopia), and destroys systemic function which is necessary to maintain
life (e.g., corneal injury, infection, and hypoplasia). Vitamin A deficiency can lead
to animal death.Vitamin A functions in reproduction and embryonic development. Vitamin A
plays an important role in the reproductive process of sperm production and ovula tion, but its biochemical basis is unclear. Vitamin A plays a key role in the develop ment of embryos and organism and maintenance of tissue function. The main organs
affected by vitamin A deficiency are the heart, eye tissue, circulatory system, geni tourinary system, and respiratory system. Vitamin A is necessary for embryonic
development.Vitamin A functions on immune function. The lymphoid organs, cell distribu tion, histology, lymphocytes, and other characteristics will change when the ani mals lack vitamin A. Vitamin A deficiency can lead to immune function decrease,
induce inflammation, and exacerbate inflammatory symptomsVitamin A functions in dermatology. Vitamin A plays an important role in main taining healthy skin. Vitamin A deficiency disrupts human keratin cell terminal dif ferentiation and makes the skin rough, dry, scaly, and clogged It is reported that vitamin A can degrade malignant melanoma and T-cell lymphoma
epidermal transfer, reduce the oil secretion of the common acne and the number of
bacteria in the epidermis and capillaries, and inhibit immune response of monocytes
and neutrophils.Vitamin A plays an important role as an important function material in the body
system, such as hematopoietic function, bone development, tumor prevention, and
so on. Therefore, supplement of vitamin A is necessary for health requirements
Clinical Use
Principal dietary sources of vitamin A are milk fat
(cheese and butter) and eggs. Since it is stored in the
liver, inclusion of liver in the diet also provides vitamin
A. A plant pigment, carotene, is a precursor for vitamin
A and is present in highly pigmented vegetables, such as
carrots, rutabaga, and red cabbage.
An early sign of hypovitaminosis A is night blindness.
This condition is related to the role of vitamin A as
the prosthetic group of the visual pigment rhodopsin.
The night blindness may progress to xerophthalmia
(dryness and ulceration of the cornea) and blindness.
Other symptoms of vitamin A deficiency include cessation
of growth and skin changes due to hyperkeratosis.
Since vitamin A is a fat-soluble vitamin, any disease
that results in fat malabsorption and impaired liver storage
brings with it the risk of vitamin A deficiency; these
conditions include biliary tract disease, pancreatic disease,
sprue, and hepatic cirrhosis. One group at great
risk are children from low-income families, who are
likely to lack fresh vegetables (carotene) and dairy
products (vitamin A) in the diet.
Side effects
Acute hypervitaminosis A results in drowsiness,
headache, vomiting, papilledema, and a bulging fontanel
in infants. The symptoms of chronic toxicity include
scaly skin, hair loss, brittle nails, and hepatosplenomegaly.
Anorexia, irritability, and swelling of
the bones have been seen in children. Retardation of
growth also may occur. Liver toxicity has been associated
with excessive vitamin A intake. Vitamin A is teratogenic
in large amounts, and supplements should not
be given during a normal pregnancy. The IOM has reported
the UL of vitamin A to be 3,000 μg/day.
Safety Profile
Moderately toxic by
ingestion. Human teratogenic effects by
ingestion: developmental abnormalities of
the craniofacial area and urogenital system.
An experimental teratogen. Experimental
reproductive effects. Human mutation data
reported. When heated to decomposition it
emits acrid smoke and irritating fumes.
Purification Methods
Purify retinol by chromatography on columns of water-deactivated alumina and elute with 3-5% acetone in hexane. Separate the isomers by TLC plates on silica gel G, developed with pet ether (low boiling)/methyl heptanone (11:2). Store it in the dark, under N2, at 0o, or in Et2O, Me2CO or EtOAc. [See Gunghaly et al. Arch Biochem Biophys 38 75 1952, Beilstein 6 IV 4133.]
Toxicity evaluation
The exact mechanism leading to toxicity is not known. Both
acute and chronic toxicity may occur.
Acute and Short-Term Toxicity (or Exposure)
Human
Acute toxicity is uncommon in adults. However, vitamin A
ingestions of greater than 1 million IU in adults and greater
than 300 000 IU in children have resulted in the development
of increased intracranial pressure (symptoms described include
headache, dizziness, vomiting, visual changes, and bulging
fontanel in infants). Acute ingestions of greater than 12 000 IU
per kilogram are also considered toxic.
Chronic Toxicity (or Exposure)
Human
Toxicity is more frequently seen with chronic ingestion of
high doses of 30 000–50 000 IU per day. Vitamin A toxicity in
children develops following chronic ingestion of 410 times
the recommended daily allowance for weeks to months.
Malnutrition and individual tolerance may also be factors in
predisposition to toxicity. Signs and symptoms of toxicity
include vomiting, anorexia, agitation, fatigue, double vision,
headache, bone pain, alopecia, skin lesions, increased intracranial
pressure, and papilledema. Hepatic toxicity typically requires months or years of daily high doses of vitamin A.
There are no known cases of vitamin A toxicity associated with
beta-carotene ingestion.
Check Digit Verification of cas no
The CAS Registry Mumber 68-26-8 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 8 respectively; the second part has 2 digits, 2 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 68-26:
(4*6)+(3*8)+(2*2)+(1*6)=58
58 % 10 = 8
So 68-26-8 is a valid CAS Registry Number.
InChI:InChI=1/C20H30O/c1-16(8-6-9-17(2)13-15-21)11-12-19-18(3)10-7-14-20(19,4)5/h6,8-9,11-13,21H,7,10,14-15H2,1-5H3/b9-6u,12-11+,16-8+,17-13u
68-26-8Relevant articles and documents
Human and rodent aldo-keto reductases from the AKR1B subfamily and their specificity with retinaldehyde
Ruiz, F. Xavier,Moro, Armando,Gallego, Oriol,Ardèvol, Albert,Rovira, Carme,Petrash, J. Mark,Parés, Xavier,Farrés, Jaume
, p. 199 - 205 (2011)
NADP(H)-dependent cytosolic aldo-keto reductases (AKR) are mostly monomeric enzymes which fold into a typical (α/β)8-barrel structure. Substrate specificity and inhibitor selectivity are determined by interaction with residues located in three highly variable loops (A, B, and C). Based on sequence identity, AKR have been grouped into families, namely AKR1-AKR15, containing multiple subfamilies. Two human enzymes from the AKR1B subfamily (AKR1B1 and AKR1B10) are of special interest. AKR1B1 (aldose reductase) is related to secondary diabetic complications, while AKR1B10 is induced in cancer cells and is highly active with all-trans-retinaldehyde. Residues interacting with all-trans-retinaldehyde and differing between AKR1B1 and AKR1B10 are Leu125Lys and Val131Ala (loop A), Leu301Val, Ser303Gln, and Cys304Ser (loop C). Recently, we demonstrated the importance of Lys125 as a determinant of AKR1B10 specificity for retinoids. Residues 301 and 304 are also involved in interactions with substrates or inhibitors, and thus we checked their contribution to retinoid specificity. We also extended our study with retinoids to rodent members of the AKR1B subfamily: AKR1B3 (aldose reductase), AKR1B7 (mouse vas deferens protein), AKR1B8 (fibroblast-growth factor 1-regulated protein), and AKR1B9 (Chinese hamster ovary reductase), which were tested against all-trans isomers of retinaldehyde and retinol. All enzymes were active with retinaldehyde, but with kcat values (0.02-0.52 min -1) much lower than that of AKR1B10 (27 min-1). None of the enzymes showed oxidizing activity with retinol. Since these enzymes (except AKR1B3) have Lys125, other residues should account for retinaldehyde specificity. Here, by using site-directed mutagenesis and molecular modeling, we further delineate the contribution of residues 301 and 304. We demonstrate that besides Lys125, Ser304 is a major structural determinant for all-trans-retinaldehyde specificity of AKR1B10.
Iron-Catalyzed Vinylzincation of Terminal Alkynes
Hu, Meng-Yang,Huang, Qiang,Su, Yu-Xuan,Sun, Wei,Wang, Wei-Na,Zhu, Shou-Fei
, (2022/01/08)
Organozinc reagents are among the most commonly used organometallic reagents in modern synthetic chemistry, and multifunctionalized organozinc reagents can be synthesized from structurally simple, readily available ones by means of alkyne carbozincation. However, this method suffers from poor tolerance for terminal alkynes, and transformation of the newly introduced organic groups is difficult, which limits its applications. Herein, we report a method for vinylzincation of terminal alkynes catalyzed by newly developed iron catalysts bearing 1,10-phenanthroline-imine ligands. This method provides efficient access to novel organozinc reagents with a diverse array of structures and functional groups from readily available vinylzinc reagents and terminal alkynes. The method features excellent functional group tolerance (tolerated functional groups include amino, amide, cyano, ester, hydroxyl, sulfonyl, acetal, phosphono, pyridyl), a good substrate scope (suitable terminal alkynes include aryl, alkenyl, and alkyl acetylenes bearing various functional groups), and high chemoselectivity, regioselectivity, and stereoselectivity. The method could significantly improve the synthetic efficiency of various important bioactive molecules, including vitamin A. Mechanistic studies indicate that the new iron-1,10-phenanthroline-imine catalysts developed in this study have an extremely crowded reaction pocket, which promotes efficient transfer of the vinyl group to the alkynes, disfavors substitution reactions between the zinc reagent and the terminal C–H bond of the alkynes, and prevents the further reactions of the products. Our findings show that iron catalysts can be superior to other metal catalysts in terms of activity, chemoselectivity, regioselectivity, and stereoselectivity when suitable ligands are used.
Retinal-based polyene fluorescent probe for selectively detection of Cu2+ in physiological saline and serum
Li, Yang,Lan, Haichuang,Yan, Xia,Shi, Xiaotao,Liu, Xiao,Xiao, Shuzhang
, (2019/11/02)
Retinal is a flexible natural chromophore and widely present in organisms. The slender conjugated polyene structure retinal is conducive to entering protein structure. In this work, a novel turn-on fluorescent probe for Cu2+ based on retinal and phenylenediamine was designed and synthesized. The probe achieved recognition of copper ions in human serum complex protein environment. Furthermore, the high sensitivity, selectivity for Cu2+ and the sensing mechanism was also investigated.
Mimicking light-sensing chromophore in visual pigments and determination isomerization site
Li, Yang,Lan, Haichuang,Yan, Xia,Shi, Xiaotao,Liu, Xiao,Xiao, Shuzhang
, (2020/01/02)
Three retinal derivatives are designed and synthesized under the inspiration of natural visual pigments. The retinal derivative V3 (retinal-phenylenediamine) is able to respond sensitively to visual light in the absence of a protein environment through isomerization and deprotonation. The response process is applied to verification of information security.
Preparation method of tretinoin
-
Paragraph 0020; 0029-0030, (2020/05/11)
The invention discloses a preparation method of tretinoin. The method comprises the following steps: 1) hydrolyzing vitamin A acetate under an alkaline condition to obtain vitamin A; and 2) in an oxygen atmosphere, carrying out an oxidation reaction on the vitamin A in an ionic liquid bis-(3-methyl-1-imidazole)ethylene tetrafluoroborate under the catalytic action of RuCl2(PPh3)3 to obtain tretinoin. The method has the advantages of mild reaction conditions, easily available reaction raw materials, no need of purification of intermediates, reaction yield of up to 90%, purity of 99%, and good industrial application prospect.
Method for preparing vitamin A and vitamin A ester
-
, (2020/04/17)
The invention provides a novel method for preparing vitamin A and vitamin A ester by taking farnesol as a raw material. The method comprises the following steps: carrying out oxidation reaction on farnesol and oxygen under the action of a catalyst and a cocatalyst to generate farnesal; carrying out dehydrogenation reaction on farnesal to generate dehydrofarnesal; carrying out cyclization reactionon the dehydrofarnesal under the catalysis of acid to generate a cyclized intermediate; carrying out a reaction on the cyclized intermediate with chloroisopentenol to generate vitamin A; carrying outan esterification reaction on vitamin A to generate vitamin A ester. The method avoids the defects of an existing process, and the process line is economical and effective.
Preparation method of vitamin A and vitamin A ester
-
, (2020/04/02)
The invention provides a novel method for preparing vitamin A and vitamin A ester with farnesene as a raw material. The method comprises the following steps: reacting farnesene with acetoacetate underthe action of a catalyst to obtain farnesyl keto ester; carrying out a cyclization reaction and a dehydrogenation reaction on farnesene acetone, and then reacting a reaction product with vinyl magnesium halide to generate vinyl alcohol; carrying out a rearrangement reaction on vinyl alcohol to obtain vitamin A; and subjecting the vitamin A to an esterification reaction to obtain the vitamin A ester. The method avoids the defects of the existing processes, and the process line of the method is economical and effective.
Synthesis of C11-to-C14 methyl-shifted all-: Trans -retinal analogues and their activities on human aldo-keto reductases
Alvarez, Rosana,Barracco, Vito,De Lera, Angel R.,Domínguez, Marta,Farrés, Jaume,Jiménez, Rafael,López, Susana,Parés, Xavier,Pequerul, Raquel,Rivas, Aurea
supporting information, p. 4788 - 4801 (2020/07/13)
Human aldo-keto reductases (AKRs) are enzymes involved in the reduction, among other substrates, of all-trans-retinal to all-trans-retinol (vitamin A), thus contributing to the control of the levels of retinoids in organisms. Structure-activity relationship studies of a series of C11-to-C14 methyl-shifted (relative to natural C13-methyl) all-trans-retinal analogues as putative substrates of AKRs have been reported. The synthesis of these retinoids was based on the formation of a C10-C11 single bond of the pentaene skeleton starting from a trienyl iodide and the corresponding dienylstannanes and dienylsilanes, using the Stille-Kosugi-Migita and Hiyama-Denmark cross-coupling reactions, respectively. Since these reagents differ by the location and presence of methyl groups at the dienylorganometallic fragment, the study also provided insights into the ability of the different positional isomers to undergo cross-coupling and the sensitivity of these processes to steric hindrance. The resulting C11-to-C14 methyl-shifted all-trans-retinal analogues were found to be active substrates when tested with AKR1B1 and AKR1B10 enzymes, although relevant differences in substrate specificities were noted. For AKR1B1, all analogues exhibited higher catalytic efficiency (kcat/Km) than parent all-trans-retinal. In addition, only all-trans-11-methylretinal, the most hydrophobic derivative, showed a higher value of kcat/Km = 106 000 ± 23 200 mM-1 min-1 for AKR1B10, which is in fact the highest value from all known retinoid substrates of this enzyme. The novel structures, identified as efficient AKR substrates, may serve in the design of selective inhibitors with potential pharmacological interest. This journal is
Preparation process of vitamin A intermediate and vitamin A acetate
-
, (2019/10/23)
The invention discloses a preparation process of a vitamin A intermediate. Compared with a traditional Kuraray synthesis route, the preparation process directly carries out halogenation reaction on analcohol metal intermediate without hydrolysis in an anhydrous and oxygen-free environment, not only reduces one-step chemical reaction and shortens working procedures, but also reduces the use of reagents and solvents, at the same time also improves the utilization rate of metallization reagents, greatly reduces pollution, and improves safety and economic benefits. The invention also provides a preparation method of vitamin A acetate based on the vitamin A intermediate, and the obtained vitamin A acetate has higher purity and is easy to store.
MULTILAYERED EMULSION FILM AND METHOD FOR PREPARING THE SAME
-
, (2019/06/19)
Multilayer thin emulsion films are disclosed. Also disclosed are methods for preparing the multilayer thin emulsion films. According to the methods, an amphiphilic block polymer is used as a surfactant to form a polymer thin film at the oil/water interface, ionic lecithin is used as an auxiliary surfactant to prepare physically stable ionic oil-in-water nanoemulsions, and a layer-by-layer assembly technique is used to alternately laminate polymer thin films and nanoemulsion layers. The multilayer thin emulsion films enable slow release of active substances in specific temperature ranges and are structurally biocompatible while possessing improved capture efficiency and physically stable membrane structures. Spinodal decomposition of the multilayer thin emulsion films is induced by heating, allowing release of oils and active substances loaded into the nanoemulsions. Therefore, the multilayer thin emulsion films are expected to be useful as smart drug release materials in a variety of applications, including cosmetics, pharmaceuticals, and biotherapy.
