1. Phytol & Retinol Presented By: Diwan
M. Pharm, Pharmaceutical
Chemistry
Chemistry Of
Natural Products
2. Phytol is an acyclic diterpene alcohol that can
be used as a precursor for the manufacture of
synthetic forms of vitamin E and vitamin
K1. In ruminants, the gut fermentation of
ingested plant materials liberates phytol, a
constituent of chlorophyll, which is then
converted to phytanic acid and stored in fats. In
shark liver it yields pristane.
1. IUPAC name: 3,7,11,15-tetramethyl-hexadec-
2-en-1-ol
2. Chemical formula: C20H40O
3. Molar mass:296.539 g·mol−1
4. Colourless to yellow viscous liquid; Faint
floral aroma
5. Practically insoluble to insoluble in water
6. Soluble (in ethanol)
7. Density :0.847-0.863
Introduction
4. Elemental analysis shows that Molecular formula of phytol is: C20H40O
Phytol belongs to diterpenoid class of terpenoids
• It contains four isoprene units joins head to tail
Degree of unsaturation = x + 1 – y/2 = 21-20 =1
Hydrogenation of phytol forms dihydophytol
Phytol contain one double bond.
Structure Determination of phytol
5. On analyzing the spectra of compound 1, it appears to be
an extension of phytol by additional double bound and
methyl groups. While phytol is C-20, compound 1 is a C-
26 compound with additional CH3 at C-22, CH2 at C-16,
C-17 and C-20, at C-19 and at C-18. This compound (2E,
18E)-3,7,11,15,18- pentamethylhenicosa-2,18-dien-1-ol,
named eluptol, appears new and it is also being
reported for cholinesterase inhibitory activity for the
first time.
Structral Elucidation
6. Nature of oxygen:
• Phytol forms monoacetate derivetive with Ac2O/
Pyridine.
• Oxidation of Phytol with same no of carbon
atoms.
Phytol is an primary alcohol.
Phytol is an acyclic molecule.
C20 H 40O C20H38O (Phytenic acid)
Ac2O
Pyridine
Monoacetate
derivative of phytol
Position of double bond:
Ozonolysis
CrO3
9. 1. Phytol is likely the most abundant acyclic isoprenoid compound present in the biosphere and its degradation products
have been used as biogeochemical tracers in aquatic environments.
2. Phytol is used in the fragrance industry and used in cosmetics, shampoos, toilet soaps, household cleaners, and
detergents.
3. Phytol is also used in some Cannabis distillate vapes as a diluent . Its worldwide use has been estimated to be
approximately 0.1–1.0 metric tons per year.
4. Phytol a diterpene alcohol, in a mouse model of acute inflammation, and phytol effect on leukocyte recruitment,
cytokines levels, and oxidative stress. The anti‐inflammatory activities of phytol were assessed by measuring paw edema
induced by different inflammatory agents (e.g., λ‐carrageenan, compound 48/80, histamine, serotonin, bradykinin, and
prostaglandin E2 [PGE2])
Applications
10. Retinol
Retinol, also known as vitamin A1-alcohol, is a vitamin in the vitamin A family found in food and used as
a dietary supplement. As a supplement it is ingested 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 a couple of times a year. It is also used to reduce the risk of
complications in those who have measles. It is used by mouth or injection into a muscle.
Retinol at normal doses is well tolerated. High doses may result in an enlarged liver, dry skin,
or hypervitaminosis A. High doses during pregnancy may result in harm to the baby. It is converted in
the body 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. It is on the World Health
Organization's List of Essential Medicines. Retinol is available as a generic medication and over the
counter.
Formula: C20H30O
Molar mass; 286.4516 g·mol−1
11. Vitamin A is found in many foods, including carrot, broccoli, sweet potato, pumpkin, etc.
Vitamin A has multiple functions: it is important for growth and development, for the maintenance of the
immune system and good vision.
It also helps to maintain the health of the mucous membrane and the skin, so many anti-aging creams
contain vit. A
A deficiency of vitamin A causes night blindness, as well as dry eyes and skin.
Vitamin A ( Retinol)
12. Elemental analysis shows that Molecular formula of retinol is: C20H30O
Retinol belongs to diterpenoid class of terpenoids
• It contains four isoprene units joins head to tail
Degree of unsaturation = x + 1 – y/2 = 21-15 =6
Nature of Oxygen: Vitamin A on reaction with p-nitrobenzoic acid leads to formation of ester.
• This confirms vitamin A contains a hydroxyl group.
C20H30O Formation of ester
Structure Determination of Retinol
p-NO2C6H4COOH
13. Analysis of unsaturation:
Vitamin A reacts with five molecule of Hydrogen and form perhydrovitamin A
Therefore it contains five C=C .
Presence of one ring: The deoxygenated parent saturated hydrocarbon of vitamin A is C20H40, which
corresponds to CnH2n molecular formula. This proves the presence of one ring in vitamin A.
Ozonolysis: Ozonolysis of Vitamin A produces one molecule of gernoic acid. It was known to chemists that
β-ionone also forms gernoic acid on ozonolysis.
Therefore, vitamin A may contain one β-ionone unit.
Structure Determination of Retinol
16. 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
Biosynthesis
19. 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
vitamin A deficiency is night-blindness followed by decreased visual acuity.
Many of the non-visual functions of vitamin A are mediated by retinoic acid, which regulates gene
expression by activating nuclear retinoic acid receptors. The non-visual functions of vitamin A 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 vitamin A in their diet.
Chemistry
20. The retinal molecule inside an opsin protein
absorbs a photon of light. Absorption of the
photon causes retinal to change from its 11-cis-
retinal isomer into its all-trans-retinal isomer.
This change in shape of retinal pushes against the
outer opsin protein to begin a signal cascade,
which may eventually result in chemical signaling
being sent to the brain as visual perception.
The retinal is re-loaded by the body so that
signaling can happen again.
Chemistry of vision
21. Vitamin A is a fat soluble Vitamin.
Present only in foods of animal origin
Its provitamins carotenes are found in plants
Chemistry:
Retinol, retinal and retinoic acid are termed as vitamers of Vitamin A
It is a primary alcohol containing β-ionone ring
The side chain has two isoprenoid units, four double bonds and one hydroxyl group
Retinols present in animal tissues as retinyl ester with long chain.
Retinol (Vitamin A Alcohol)
22. 1. This is an aldehyde form obtained by the oxidation of retinol.
2. Retinal and retinol are interconvertible Retinal
Retinal (vit. A Aldehyde)
23. 1. This is produced by the oxidation of retinal
2. Retinoic acid cannot give rise to the formation of retinal or retinol
Retinoic acid (vit. A acid)
24. 1. All the compounds with vitamin A activity are referred as retinoids
2. They are poly-isoprenoid compounds having beta-ionone ring system
3. The retinal may be reduced to retinol by retinal reductase and it is reversible
4. Retinal is oxidized to retinoic acid , which cannot be converted to the other forms
Retinol (alcohol) Retinal (aldehyde)
Reductase
NAD+ NADH + H+
Retinoic acid
25. Medical Uses:
Retinol is used to treat vitamin A deficiency.
Three approaches may be used when
populations have low vitamin A levels:
Through dietary modification involving the
adjustment of menu choices of affected
persons from available food sources to
optimize vitamin A content.
Enriching commonly eaten and affordable
foods with vitamin A, a process called
fortification. It 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 vitamin A to the
targeted deficient population, a method
known as supplementation.
26. Phytol
1. https://en.wikipedia.org/wiki/Phytol#:~:text=Phytol%20is%20an%20acy
clic%20diterpene,acid%20and%20stored%20in%20fats.
2. ‘Mach Jennifer’ Phytol from Degradation of Chlorophyll Feeds
Biosynthesis of Tocopherols Article in The Plant Cell · October 2015
3. Netscher, Thomas (2007). "Synthesis of Vitamin E". In Litwack, Gerald
(ed.). Vitamin E. Vitamins & Hormones. 76. doi:10.1016/S0083-
6729(07)76007-7. ISBN 978-0-12-373592-8. PMID 17628175
4. https://pubchem.ncbi.nlm.nih.gov/compound/Phytol
Retinol
1. https://en.wikipedia.org/wiki/Retinol#:~:text=Retinol%20is%20synthesi
zed%20from%20the,double%20bond%2C%20creating%20an%20epoxid
e.&text=Retinal%20is%20then%20reduced%20to,that%20is%20depend
ent%20on%20NAD H.
2. World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR
(eds.). WHO Model Formulary 2008. World Health Organization.
p. 500. hdl:10665/44053.
3. Amer M, Maged M: Cosmeceuticals versus pharmaceuticals. Clin
Dermatol. 2009, 27 (5): 428-430. 10.1016/j.clindermatol.2009.05.004.
References
