PRODUCTS

RETINOL

CAS NUMBER: 68-26-8

EC NUMBER: 200-683-7

MOLECULAR WEIGHT: 286.5

MOLECULAR FORMULA: C20H30O

IUPAC NAME: (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraen-1-ol

Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family found in food and used as a dietary supplement.
As a supplement Retinol is used to treat and prevent vitamin A deficiency, especially that which results in xerophthalmia.
In regions where deficiency is common, a single large dose is recommended to those at high risk twice a year.

Retinol is also used to reduce the risk of complications in measles patients.
Retinol is taken by mouth or by injection into a muscle.
Retinol at normal doses is well tolerated.

The body converts retinol to retinal and retinoic acid, through which it acts.
Dietary sources include fish, dairy products, and meat.

Retinol was discovered in 1909, isolated in 1931, and first made in 1947.
Retinol is on the World Health Organization's List of Essential Medicines.
Retinol is available as a generic medication and over the counter.

MEDICAL USES:
Retinol is used to treat Vitamin A deficiency.
Three approaches may be used when populations have low Retinol levels:

-Through dietary modification involving the adjustment of menu choices of affected persons from available food sources to optimize Retinol content.

-Enriching commonly eaten and affordable foods with Retinol, a process called fortification.
Retinol involves addition of synthetic Vitamin A to staple foods like margarine, bread, flours, cereals and other infant formulae during processing

-By giving high-doses of Retinol to the targeted deficient population, a method known as supplementation.

Biological Roles:
Retinol or other forms of vitamin A are needed for eyesight, maintenance of the skin, and human development.
Other than for vision, the active compound is all-trans-retinoic acid, synthesized from retinal, in turn synthesized from retinol.

Embryology:
Retinoic acid via the retinoic acid receptor influences the process of cell differentiation, hence, the growth and development of embryos.
During development, there is a concentration gradient of retinoic acid along the anterior-posterior (head-tail) axis.
Cells in the embryo respond to retinoic acid differently depending on the amount present.
For example, in vertebrates, the hindbrain transiently forms eight rhombomeres and each rhombomere has a specific pattern of genes being expressed.
If retinoic acid is not present the last four rhombomeres do not develop.
Instead, rhombomeres 1–4 grow to cover the same amount of space as all eight would normally occupy.
Retinoic acid has its effects by turning on a differential pattern of Homeobox (Hox) genes that encode different homeodomain transcription factors which in turn can turn on cell type specific genes.
Deletion of the Homeobox (Hox-1) gene from rhombomere 4 makes the neurons growing in that region behave like neurons from rhombomere 2.
Retinoic acid is not required for patterning of the retina as originally proposed, but retinoic acid synthesized in the retina is secreted into surrounding mesenchyme where it is required to prevent overgrowth of perioptic mesenchyme which can cause microphthalmia, defects in the cornea and eyelid, and rotation of the optic cup.

Stem Cell Biology:
Retinoic acid is an influential factor used in differentiation of stem cells to more committed fates, echoing retinoic acid's importance in natural embryonic developmental pathways.
Retinol is thought to initiate differentiation into a number of different cell lineages by unsequestering certain sequences in the genome.
Retinol has numerous applications in the experimental induction of stem cell differentiation; amongst these are the differentiation of human embryonic stem cells to posterior foregut lineages and also to functional motor neurons.

Retinol's Vision:
Main article: visual cycle
Retinol is converted by the protein RPE65 within the retinal pigment epithelium into 11-cis-retinal.

This molecule is then transported into the photoreceptor cells of the retina, where it acts as a light-activated molecular switch within opsin proteins that activates a complex cascade called the visual cycle.
This cycle begins with 11-cis retinal absorbing light and isomerizing into all-trans retinal.

The change in shape of the molecule after absorbing light in turn changes the configuration of the complex protein rhodopsin, the visual pigment used in low light levels.
This represents the first step of the visual cycle.
This is why eating foods rich in Retinol is often said to allow an individual to see in the dark, although the effect they have on one's vision is negligible.

Night blindness, the inability to see well in dim light, is associated with a deficiency of Retinol.
At first, the most light sensitive (containing more retinal) protein rhodopsin is influenced.

Less pigmented retinal iodopsins (three forms/colors in humans), responsible for color vision and sensing relatively high light intensities (day vision), are less impaired at early stages of the Retinol deficiency.
All these protein-pigment complexes are located in the light-sensing cells in eye's retina.
When stimulated by light, rhodopsin splits into a protein and a cofactor: opsin and all-trans-retinal (a form of vitamin A). The regeneration of active rhodopsin requires opsin and 11-cis-retinal.
The regeneration of 11-cis-retinal occurs in vertebrates via a sequence of chemical transformations that constitute "the visual cycle" and which occurs primarily in the retinal pigmented epithelial cells.
Without adequate amounts of retinol, regeneration of rhodopsin is incomplete and night blindness occurs.

Glycoprotein Synthesis:
Glycoprotein synthesis requires adequate Retinol status.
In severe Retinol deficiency, lack of glycoproteins may lead to corneal ulcers or liquefaction.

Immune System:
Retinol is essential to maintain intact epithelial tissues as a physical barrier to infection; it is also involved in maintaining a number of immune cell types from both the innate and acquired immune systems.
These include the lymphocytes (B-cells, T-cells, and natural killer cells), as well as many myelocytes (neutrophils, macrophages, and myeloid dendritic cells).

Skin:
Deficiencies in Retinol have been linked to an increased susceptibility to skin infection and inflammation.
Retinol appears to modulate the innate immune response and maintains homeostasis of epithelial tissues and mucosa through its metabolite, retinoic acid (RA).
As part of the innate immune system, toll-like receptors in skin cells respond to pathogens and cell damage by inducing a pro-inflammatory immune response which includes increased RA production.
The epithelium of the skin encounters bacteria, fungi and viruses.
Keratinocytes of the epidermal layer of the skin produce and secrete antimicrobial peptides (AMPs).
Production of AMPs resistin and cathelicidin, are promoted by RA.
Another way that Retinol helps maintain a healthy skin and hair follicle microbiome, especially on the face, is by reduction of sebum secretion, which is a nutrient source for bacteria.

Red Blood Cells:
Retinol may be needed for normal red blood cell formation; deficiency causes abnormalities in iron metabolism.
Retinol is needed to produce the red blood cells from stem cells through retinoid differentiation.

NUTRITION:
This vitamin plays an essential role in vision, particularly night vision, normal bone and tooth development, reproduction, and the health of skin and mucous membranes (the mucus-secreting layer that lines body regions such as the respiratory tract).
Retinol also acts in the body as an antioxidant, a protective chemical that may reduce the risk of certain cancers.

There are two sources of dietary Retinol.
Active forms, which are immediately available to the body are obtained from animal products.
These are known as retinoids and include retinaldehyde and retinol.

Precursors, also known as provitamins, which must be converted to active forms by the body, are obtained from fruits and vegetables containing yellow, orange and dark green pigments, known as carotenoids, the most well-known being β-carotene.
For this reason, amounts of Retinol are measured in Retinol Equivalents (RE).

One RE is equivalent to 0.001 mg of retinol, or 0.006 mg of β-carotene, or 3.3 International Units of Retinol.
In the intestine, Retinol is protected from being chemically changed by vitamin E.

Retinol is fat-soluble and can be stored in the body.
Most of the Retinol consumed is stored in the liver.
When required by a particular part of the body, the liver releases some Retinol, which is carried by the blood and delivered to the target cells and tissues.

Deficiency:
Retinol deficiency is common in developing countries but rarely seen in developed countries.
Approximately 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of Retinol.
Retinol deficiency in expecting mothers increases the mortality rate of children shortly after childbirth.
Night blindness is one of the first signs of Retinol deficiency.
Retinol deficiency contributes to blindness by making the cornea very dry and damaging the retina and cornea.

Sources:
Retinoids are found naturally only in foods of animal origin.
Each of the following contains at least 0.15 mg of retinoids per 1.75–7 oz (50–198 g):
*Cod liver oil

*Butter

*Liver (beef, pork, chicken, fish)

*Eggs

*Cheese

*Milk

Retinol's Chemistry:
Many different geometric isomers of retinol, retinal and retinoic acid are possible as a result of either a trans or cis configuration of four of the five double bonds found in the polyene chain.

The cis isomers are less stable and can readily convert to the all-trans configuration (as seen in the structure of all-trans-retinol shown at the top of this page).
Nevertheless, some cis isomers are found naturally and carry out essential functions.

For example, the 11-cis-retinal isomer is the chromophore of rhodopsin, the vertebrate photoreceptor molecule. Rhodopsin is composed of the 11-cis-retinal covalently linked via a Schiff base to the opsin protein (either rod opsin or blue, red or green cone opsins).
The process of vision relies on the light-induced isomerisation of the chromophore from 11-cis to all-trans resulting in a change of the conformation and activation of the photoreceptor molecule.

One of the earliest signs of Retinol deficiency is night-blindness followed by decreased visual acuity.
Many of the non-visual functions of Retinol are mediated by retinoic acid, which regulates gene expression by activating nuclear retinoic acid receptors.
The non-visual functions of Retinol are essential in the immunological function, reproduction and embryonic development of vertebrates as evidenced by the impaired growth, susceptibility to infection and birth defects observed in populations receiving suboptimal Retinol in their diet

SYNTHESIS OF Retinol:
-Biosynthesis:
Retinol is synthesized from the breakdown of β-carotene.
First, the β-carotene 15-15’-monooxygenase cleaves β-carotene at the central double bond, creating an epoxide.
This epoxide is then attacked by water creating two hydroxyl groups in the center of the structure.
The cleavage occurs when these alcohols are reduced to the aldehydes using NADH.
This compound is called retinal.
Retinal is then reduced to retinol by the enzyme retinol dehydrogenase.
Retinol dehydrogenase is an enzyme that is dependent on NADH.

-Industrial Synthesis:
β-carotene can be extracted from fungus Blakeslea trispora, marine algae Dunaliella salina or genetically modified bacteria of the genus Sphingomonas, or else via total synthesis using either a method developed by BASF or a Grignard reaction utilized by Hoffman-La Roche.
The world market for synthetic retinol is primarily for animal feed, leaving approximately 13% for a combination of food, prescription medication and dietary supplement use.
The first industrialized synthesis of retinol was achieved by the company Hoffmann-La Roche in 1947.
In the following decades, eight other companies developed their own processes. β-ionone, synthesized from acetone, is the essential starting point for all industrial syntheses.
Each process involves elongating the unsaturated carbon chain.
Pure retinol is extremely sensitive to oxidization and is prepared and transported at low temperatures and oxygen-free atmospheres.
When prepared as a dietary supplement or food additive, retinol is stabilized as the ester derivatives retinyl acetate or retinyl palmitate.
Prior to 1999, three companies, Roche, BASF and Rhone-Poulenc controlled 96% of global Retinol sales.
In 2001, the European Commission imposed total fines of 855.22 Euros on these and five other companies for their participation in eight distinct market-sharing and price-fixing cartels that dated back to 1989.
Roche sold its vitamin division to DSM in 2003.
DSM and BASF have the major share of industrial production.

Retinol can do a lot for your skin: aging support, acne relief, and overall skin rejuvenation.
Derived from Retinol, this multitasking skin care ingredient is a form of retinoid.

What Does Retinol Do For Skin?
From breakouts to sun damage, retinol can help address a variety of skin concerns.

Acne:
Retinol helps keep pores clear by reducing the buildup of skin cells.
Plus, it can block inflammation pathways in the skin.
In a nutshell, that means retinol doesn’t only help reduce the number of breakouts you have.
Retinol can also minimize the redness and swelling that comes with them.

Aging support:
Skin cells naturally turn over, revealing fresh cells underneath.
Retinol helps speed up this turnover process and promote brighter, smoother skin.
Retinol also goes deeper into the skin to encourage collagen production and further plump the skin.

Sun damage:
Faster skin cell turnover can also help improve skin tone.
This can have particular benefit when you have signs of sun damage, like:
-wrinkles

-fine lines

-hyperpigmentation

Retinol can even strengthen the skin, helping protect it against further environmental damage.

The extras:
A buildup of dead skin cells can leave your skin drier than you’d like.
Removing those dead cells, with the help of retinol, can lead to more hydrated skin.
Retinol can also help treat keratosis pilaris by smoothing rough and bumpy skin textures.

Retinol is an over-the-counter cosmetic ingredient that’s become popular over recent years for helping to soften existing wrinkles and fight against the formation of new ones.
Many people use creams containing retinol to help reduce signs of ageing, but its array of fantastic uses don’t end there.
Due to retinol’s revitalising qualities, it can also be used to help improve the appearance of a number of other skin imperfections.

Retinol is a derivative of vitamin A.
Retinol helps to smooth imperfections and reduce the appearance of wrinkles, as well as being great for helping to reduce the appearance of dark spots, blotches and sun damage.

Retinol is a type of retinoid, a derivative of vitamin A, used for anti-aging and found in many skin care products.
Though many people are under the impression that retinol is an exfoliant, it’s an antioxidant.

5 Main Benefits of Retinol:
There are many benefits to retinol, but there are 5 main reasons why people buy and use retinol:

*Retinol Can Clear Your Acne

*Retinol Can Fight Signs Of Aging

*Retinol Can Help Even Skin Tone

*Retinol Is Cost-Effective

*Available In Prescription Or Over-The-Counter

Retinol is the fat soluble vitamin retinol.
Retinol binds to and activates retinoid receptors (RARs), thereby inducing cell differentiation and apoptosis of some cancer cell types and inhibiting carcinogenesis.
Retinol plays an essential role in many physiologic processes, including proper functioning of the retina, growth and differentiation of target tissues, proper functioning of the reproductive organs, and modulation of immune function.

Retinol is a retinol in which all four exocyclic double bonds have E- (trans-) geometry.
Retinol has a role as a human metabolite, a mouse metabolite and a plant metabolite.
Retinol is a retinol and a vitamin A.

Retinol is a fat soluble vitamin necessary for health, deficiency of which can cause disorders of vision, skin, bone and immunity.
The recommended daily allowance for Retinol is 300 to 700 μg for children and approximately 700 to 900 μg for adults, amounts which can be provided by a normal diet.

PHYSICAL PROPERTIES:

-Molecular Weight: 286.5

-XLogP3: 5.7

-Exact Mass: 286.229665576

-Monoisotopic Mass: 286.229665576

-Topological Polar Surface Area: 20.2 Å²

-Physical Description: Retinol appears as yellow crystals or orange solid.

-Color/Form: Solvated crystals from polar solvents, such as methanol or ethyl formate

-Boiling Point: 137-138 °C

-Melting Point: 63.5 °C

-Solubility: 0.671 mg/L

-Vapor Pressure: 7.5X10-8 mm Hg

-LogP: 5.68

-Henry's Law constant: 1.2X10-4 atm-cu m/mol

-Index of refraction: 1.6410 at 20 °C/D

Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family found in food and used as a dietary supplement.
As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xerophthalmia.
In regions where deficiency is common, a single large dose is recommended to those at high risk twice a year.

Retinol is also used to reduce the risk of complications in measles patients.
Retinol is taken by mouth or by injection into a muscle.

CHEMICAL PROPERTIES:

-Hydrogen Bond Donor Count: 1

-Hydrogen Bond Acceptor Count: 1

-Rotatable Bond Count: 5

-Heavy Atom Count: 21

-Formal Charge: 0

-Complexity: 496

-Isotope Atom Count: 0

-Defined Atom Stereocenter Count: 0

-Undefined Atom Stereocenter Count: 0

-Defined Bond Stereocenter Count: 4

-Undefined Bond Stereocenter Count: 0

-Covalently-Bonded Unit Count: 1

-Compound Is Canonicalized: Yes

SYNONYMS:

Retinol
Vitamin A
all-trans-Retinol
Vitamin A1
Alphalin
Axerophthol
Afaxin
Vitamin A alcohol
Oleovitamin A
Chocola A
Alphasterol
Apostavit
Aquasynth
Biosterol
Epiteliol
Ophthalamin
Agiolan
Agoncal
Anatola
Myvpack
Prepalin
Testavol
Veroftal
Aoral
Apexol
Avibon
Avitol
Axerol
Dofsol
trans-retinol
Vaflol
Vitpex
Vogan
Disatabs Tabs
Lard Factor
all-trans-Retinyl alcohol
Bentavit A
Dohyfral A
Alcovit A
Anatola A
Vogan-Neu
A-Mulsal
Plivit A
Vi-Alpha
A-Vitan
All-trans retinol
Atars
Vafol
all-trans-Vitamin A alcohol
Retrovitamin A
Homagenets Aoral
A-Sol
Hi-A-Vita
Sehkraft A
Vitamin A1 alcohol
all-trans-Vitamin A
A-Vi-Pel
Vi-Dom-A
Super A
Anti-infective vitamin
Solu-A
Nio-A-Let
Vio-A
Antixerophthalmic vitamin
Del-VI-A
Vitavel A
Thalasphere
beta-Retinol
trans-Vitamin A alcohol
Vitamin A alcohol, all-trans-
Vitamin A1, all-trans-
Retinol, all trans-
all-trans-Vitamin A1
Vitamin A Oil
Vi-a
.beta.-Retinol
(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraen-1-ol
(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-ol
Vitamin A1 alcohol, all-trans-
(all-E)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol
2,4,6,8-Nonatetraen-1-ol, 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-
Axerophtholum
Wachstumsvitamin
Vitaminum A
Vitamine A
Vitavel-A
VITAMIN A
Cylasphere
Retinolo
Retinolum
Hydrovit A
Retinolum
3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol
Ro-a-vit
tROL
Vitamin A alcohol (VAN)
Antixerophthalmisches Vitamin
Aquasol A Parenteral
Vi-alpha; Vi-alpha
Rovimix A 500
9-cis retinol
Vitamin A1 alcohol, all trans
Retinol solution
Retinol (Vit A)
[11,12-3H]-Retinol
9-cis,13-cis-Retinol
Vitamin A (USP)
Vitamin A
Retin-11,12-t2-ol (9CI)
Tegosphere VitA
.alpha.sterol
b-Retinol
.alpha.lin
Retinyl A
trans-Retinol acid (Vitamin A)
1rbp
Vi-.alpha.
3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclchexen-1-yl)-2,4,6,8-nonatetraen-1-ol
(9Z)-Retinol
Retinol-(cellular-retinol-binding-protein)
all-trans vitamin A alcohol
3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonate-traen-1-ol
3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol, (all-E)-
Alcohol 9,13-dimethyl-7-(1,1,5-trimethyl-6-cyclohexen-5-yl)-7,9,11,13-nonatetraen-15-ol
all-trans-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol
4-06-00-04133 (Beilstein Handbook Reference)
Retinol, all-trans- (8CI)
Vitamin A|||Retinoid analogues
Zinc-ethylenebis(dithiocarbamate)
all-trans-13,14-Dihydro retinol
Pharmakon1600-01501203
(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetr aen-1-ol
3,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol
2,6,8-Nonatetraen-1-ol, 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-
3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol, all (E)-
(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-1-nona-2,4,6,8-tetraenol
(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraen-1-ol
(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraen-1-ol
(2Z,4Z,6Z,8Z)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetren-1-ol