terpenoids & volatile oils - wordpress.com origin of terpenoids 5 terpenoids & volatile oils...

Pharmacognosy I Lecture 8

Terpenoids & Volatile Oils

Mohammed N. Sabir

•Introduction

•Uses in Plants & Medicine

•Classes of terpenoids

•Chemistry & Biosynthetic origin

•Monoterpenoids

Terpenoids & Volatile Oils 2 17شباط، 13


Terpenoids

Widely distributed natural products, mainly found in

higher plants.

Biosynthesized from mevalonic acid via acetate β-

Plolyketide Pathway.



In Plants, they composed from dimerization and

polymerization of single isoprene (isoprenoid) units.

About 20,000 compounds related to terpenoids discovered

H3CCH3

CH3

H3CCH3

CH3

Head-to-tail conjugation



OPP OPP

Mevalonic acid

Hemiterpens C5

Isopentenyl PP(IPP) C5

Dimethylallyl PP(DMAPP) C5

C10 Monoterpenes (C10)

IPP

C15 Sesquiterpenes (C15)

IPP

C20 Diterpenes (C20)

IPP

C25 Sesterterpenes (C25)

C30 Triterpenes (C30)

Steroids (C18-C30)

C40 Tetraterpenes (C40)Carotenoids

Biosynthetic origin of terpenoids



Volatile Oils

Are terpenoids (almost mono), they are oily substances

and volatile at room temperature .



Role in Climate

Monoterpenes are emitted by forests and form that can

serve as Cloud Condensation Nuclei (CCN).

Such aerosols can increase the brightness of clouds and cool

the climate.



Functions of terpenoids in Plants

•Insect repellants

•Insect attractant (Pollinating agents)

•Defensive agents

•Plant hormones

•Signaling molecules



Medicinal Uses of terpenoids

•As flavoring agents

•Antiflactulents

•Spasmolytic

•Expectorants

•Insect repellent

•Analgesic anti-inflammatory agents

•Cough suppressants

•Local anesthetics



Acyclic Monocyclic Bicyclic

Terpenes

Hemiterpenes Monoterpenes Sesquiterpenes

Diterpenes

Triterpenes

HO

OH

Tetraterpenes



Classification of terpenoids

•Hemiterpenoids (one isoprene unit)

•Monoterpenoids (two isoprene units)

•Acyclic

•Monocyclic

•Bicyclic

•Tricyclic

•Sesquiterpenoids (three isoprene units)



Classification of terpenoids

•Diterpenoids (four isoprene units)

•Triterpenoids (six isoprene units)

•Tetraterpenoids & carotenoids (eight isoprene units)

•Meroterpenoids



CALASSFICATION

TYPE OF NUMBER OF ISOPRENE TERPENOIDS CARBON ATOMS UNITS

hemiterpenes

monoterpenes sesquiterpenes diterpenes

triterpenes

tetraterpenes

C5

C10

C15

C20

C30

C40

one

two

three four

six

eight

hemi = half di = two sesqui = one and a half tri = three tetra = four

NOTE:

sesterterpenes C25 five



Bicyclic sesquiterpenoids



ing in carbon numbers, the possibilities of cyclization

also ed.

Therefore; a wide variety of cyclic terpenoids exists.



In addition to common six-membered ring systems

such as zingiberene, a constituent of the oil from

Ginger, cyclization of one end of the chains to the

other end can lead to macrocyclic rings such as

humulene.



Sesquiterpenes are a class of terpenes that consist of

three isoprene units and have the molecular formula

C15H24.

Sesquiterpenes may be acyclic or contain rings,

including many unique combinations.



Biochemical modifications such as oxidation or

rearrangement produce the related sesquiterpenoids.



OH

Geraniol

OH

Farnesol

Squalene

Phytoene

Methanol Bisabolene Taxadiene



Nomenclature of terpenoids

-Oid suffix rather than ens

-ene suffix should be restricted for the unsaturated hydrocarbon of the class

-Isoprene units are linked head-to-tail manner

-The number of isoprene units incorporated indicate the class of the terpenoid



Named either to IUPAC (systematic) or the trivial

names…

Sometimes not only an isoprene oligomer, but rather saturated

or partially saturated isomers as well as oxygenated derivatives

such as alcohols, aldehydes, ketones, phenols, ethers and esters

are involved in the structure.



Monoterpenoids

-About 1,000 naturally occurring monoterpenoids have

been isolated from higher plants.

-Monoterpenoids are also found in secretions of

insects.



Monoterpenoids

-A characteristic feature of monoterpenoids are their

volatility and intensely pungent odor

-They are the most compounds responsible for plant

fragrance (essential oils)



Classes of monoterpenoids A-Acyclic Monoterpenoids (Myrcane sub-class)

Is the major component of Rose oil and occur in small quantities in lemon essential oils



Classes of monoterpenoids B-Cyclic Monoterpenoids 1-Monocyclic monoterpenoids (ex. p. Menthane) Found in:- -Eucalyptus oil

Used in topical preparations for the treatment of

muscle spasm (analgesic activity and in insect

repellants (Citridiol©)).



Classes of monoterpenoids

2-Bicyclic monoterpenoids

Subclasses:-

-Bornane

-Carnane

-Fenchone

-Pinane

-Thujane



H2C

CH3

OPP

PPO

H3C CH3

DMAPP

OPP

CH3

H3C CH3

GeranylPP

CH3

H3C CH3

OPP

H

Linalyl PP(Mycrane class)

Menthane

H

Bornane Pinane

ThujaneFenchone

Carnane



-Most of these monoterpenoids occur in nature as

optically pure compounds. However some of which

may present in some plants as both enantiomers.

Ex:- (+) & (-) α-Pinene in Pinus spp.



(+) alpha-pinen (-) alpha pinen

Turpentine oil



-Camphor

Is a ketone obtained from

Cinnamomum camphora

(Fam: Lauraceae)

Also Rosemarinus officinalis

Camphor = kafur

Bicyclic bornane class

CH3

O

CH3H3C

Camphor



Medicinal uses… -Local anesthetic -Anti-inflammatory -Antimicrobial -Antipruretic in conc. 0.1 – 3% -Counterirritant for neuralgia & fibrositis.



-Common colds, externally applied for the chest in cough conditions, especially in Children

-Inhalations of the aromatic vapors causes a local anesthetic action

Vicks©, Vaporub©

Extract obtained by steam distillation Synthetically, made from pinene



Cineol (eucalyptol)

Found in Eucalyptus globus and in

Cajuput, Fam: Myrtaceae

Also called cajuputol

Obtained from eucalyptus leaf oil and

other sources by steam distillation.

CH3

CH3H3C

O

Cineole



Medicinal Uses

•Flavoring agent

•Nasal inhalers for nasal congestion

•Antiseptic sprays

•Mild anesthetic for nose and throat

•Expectorant

•Analgesic



Menthol (menth-3-ol) Peppermint or Mint

Is an alcohol obtained from divers mint oils and

prepared synthetically.

It is Levorotatory (-)-menthol when natural.

The synthetic are racemic mixtures [( + )-menthol]



It is prepared form Japanese peppermint oil by freezing

to (-220oC), during which the menthol crystallizes.

The liquid portion is poured off and the crystallized menthol is

passed between filter papers and subsequently purified by

recrystallization.



Also obtained by steam distillation of the flowering

tops of Mentha arvensis, M. piperita

Fam: Lamiaceae

Synthetic racemic menthol is produced by hydrogenation of

thymol CH3

OH

CH3H3C

+H

CH3

OH

CH3H3C

Thymol Menthol Terpenoids & Volatile Oils 38 17شباط، 13


Menthol occurs as colorless, hexagonal crystals that are

usually needle like, as fused masses, or as a crystalline

powder.



Medicinal uses:-

•In concentrations ranging from 0.1-1.0%, found in

preparations used to treat minor burns and sunburns,

poison ivy rash, athletics' foot.



•In concentrations (1.0 – 16.0%) act as a counter

irritant.

•Combined with Camphor and Eucalyptus oil (Cineol) in

ointments, cough drugs, nasal sprays and inhalations to

relieve symptoms of bronchitis, sinusitis and nasal

congestion.



•Small oral doses act as carminative, however larger

doses have a depressant action on the heart.



Thymol

Is a phenol obtained from thyme oil (Thymus vulgaris)

[Lamiaceae]

It may be prepared synthetically from m-cresol or p-cymene.

OH

CH3

m-cresol

CH3

CH3H3C

p-Cymene



Thymol is an antifungal and antibacterial agent. It is

more powerful than Phenol, but it’s use is limited by its

low solubility in water and because of it’s irritation to

skin.



It’s included in topical antiseptic and analgesic

preparations in concentrations ranging from 0.1 – 1.0%

and oral gargles.



Volatile Oils

Are odorous principles found in various plant parts

Since they are volatilize upon exposure to air, they are

termed as volatile

Some times also called essential oils related to essence,

and also called ethereal oils



Spices are dried, fragrant, aromatic, or pungent plant

parts that contain volatile oils are primarily used in

food as seasoning rather than nutrition

Depending on the plant family, volatile oils may occur

in specialized secretary structures



Occurrence Family Glandular hair Lamiaceae Modified paranchymal cells Pipraceae Oil-tubes (Vittae) Apiaceae Schizogenous passages Pinaceae



They may be formed directly by the protoplasm

through decomposition of the cell wall, or by hydrolysis

of certain glycosides Part Plant Plant

All tissues Conifer

Petals Rose

Bark and Leaves Cinnamon

Glandular hair of stem and leaves

Mints

Flower petals Orange Terpenoids & Volatile Oils 51 17شباط، 13


The chemical constituents of volatile oils and spices are

divided into two broad classes, based on their

biosynthetic origin:-

1. Terpenoid (acetate, mevalonic acid)

2. Aromatic compounds (Shikimate)



Common physical properties of volatile oils

1. Characteristic odor

2. High refractive index

3. Optical activity

4. Special optical rotation

5. Immiscible with water

6. Soluble in ether, alcohol and organic solvents



Fixed oils Volatile oils Leave a permanent grease spot on paper

Can be distillated from the natural sources

Become rancid

Don’t become rancid

Sapponified with alkalis

On exposure to light they oxidize and resinify

Not volatile Volatile at room temperature

Differences between volatile oils and fixed oils



Volatile oils consist of chemical mixtures The presence of traces of the essential oils is essential for the aroma



Cinnamon Cinnamomum zeylanicum Plant part: Barks Fam: Lauraceae



Clove (Eugina) euginol

Eugina caryophyllus E. caryophylata Syzygium aromaticum Plant part: Flowers Fam: Myrtaceae



Sesquiterpenoids

Consists of three isoprene units and having the formula

C15H24.

Like monoterpenes, it may be acyclic or contain rings,

including many unique combinations.



Biochemical modifications such as oxidation or

rearrangement produce the related sesquiterpenoids.



Sesquiterpenoids

• Acyclic sesquiterpenoids

• Monocyclic sesquiterpenoids

¦Á-farnesene ¦Â-farnesene姜姜

姜姜姜

O

• Bicyclic sesquiterpenoids

OH

¦Á-eudesmol

H

H

cadineneguaiazulene



Acyclic Sesquiterpenoids

When geranyl pyrophosphate reacts with isopentenyl

pyrophosphate, the result is the 15-carbon farnesyl

pyrophosphate, which is an intermediate in the

biosynthesis of sesquiterpenes such as farnesene



farnesyl pyrophosphate

farnesene

farnesol



Oxidation can then provide sesquiterpenoids such as

farnesol .

Sesquiterpenes are found naturally in plants as

defensive agents.



Monocyclic Sesquiterpenoids

Increasing chain length and additional double bonds, the number

of possible ways that cyclization can occur is also increased, there

are a wide variety of cyclic sesquiterpenes.

姜姜zingiberene



In addition to common six-membered ring systems such as is

found in zingiberene, a constituent of the oil from ginger,

cyclization of one end of the chain to the other end can lead to

macrocyclic rings such as humulene.



Sesquiterpene lactones

The α-methylene-δ-lactone ring is essential for the

pharmacologic actions.



Example of Sesquiterpenoids

- Artemisinin

Isolated from the plant Artemisia annua.

Not all plants of this species contain artemisinin.

Used to treat multi-drug resistant strains of falciparum.



Its anti-malarial application was first described in

Zhouhou Beji Fang "The Handbook of Prescriptions for

Emergencies", edited in the middle of fourth century

by Ge Hong.



In 1972, discovered artemisinin in the leaves of

Artemisia annua



It was found that it cleared malaria parasites

from their bodies faster than any other drug in

history.



Cancer treatment is under early research and testing

lactone peroxide group which comes into contact with high

iron concentrations (common in cancerous cells), the

molecule becomes unstable and releases reactive oxygen

species. It has been shown to reduce angiogenesis and the

expression of vascular endothelial growth factor in some

tissue cultures.



Chamomile

Dried flowering tops of Matricaria recutita (Astraceae)

Bisabolol



Major constituents…

Bisabolol

Bisaboloxides

Matricin



a natural monocyclic sesquiterpene alcohol

a colorless viscous oil

almost insoluble in water

well soluble in ethanol

α-(-)-bisabolol

CH3

H3C

H3C

H3CH3C

HO



Has weak sweet floral aroma and used in various

fragrances.

Be used for hundreds of years in cosmetics because of

its perceived skin healing properties.

- spasmolytic

- anti-inflammatory

- anti-microbial



Feverfew

Dried leaves of Tanacetum parthenium

(Astraceae)

Contains Parthenolide

O

CH3

O

OH3C

CH2



The drug has anti-migraine activity



• Zingiberene

is a monocyclic sesquitepenoid which is the

predominant constituent of the oil of ginger (Zingiber

officinale), from which it gets its name.

姜姜



• The name 5-(1,5-dim--ethyl-4-hexenyl)-2-methyl-1,3-

cyclohexadiene, chemical formulaC15H24

www.herbalfire.com 13 ،17شباط Terpenoids & Volatile Oils 81


Diterpenes are composed for four isoprene units and

have the molecular formula C20H32. They derive from

geranylgeranyl pyrophosphate .

Diterpenes



geranylgeranyl pyrophosphate

Examples of diterpenes are cafestol, kahweol, cembrene

and taxadiene (precursor of taxol)



The first diterpenoids introduced were:- Abietic acid Gibberllins Podolactones Diesters of Phorbal Stevioside



Overview a mitotic inhibitor used in

cancer chemotherapy 1967, Wall and Wani Pacific yew tree, Taxus

brevifolia Bristol-Myers Squibb (BMS) taxol ---- paclitaxel ----

trademark 'Taxol‘

Taxol (Paclitaxel)



Forskolin (Colforsin)

Dried roots of the Indian herb Coleus forskohlii

(Lamiaceae)



Contains Forskolin

O

O

H3C CH3

OH

OH

OH

CH3

CH2

O CH3

O

CH3

CH3



Ginkgolides

Ginkgo is a genus of highly unusual non-flowering

plants with one extant species, G. biloba, which is

regarded as a living fossil.



Ginkgolides are biologically active terpenic lactones

present in Ginkgo biloba.

They are bicyclic diterpenoids, and there are six

lactone-rings in their skeletons.



Ginkgolide B is an extract from the cultivated leaves of

the Ginkgo Tree. Clinical studies have shown ginkgo to

benefit short term memory, cardiovascular health,

respiratory health and gastrointestinal health.



Ginkgolide B is an active platelet aggregating factor

(PAF) antagonist.

All ginkgo formulas must have adequate levels of

ginkgolide B in order to successfully increase cerebral

blood flow.



Triterpenes consist of six isoprene units and have the

molecular formula C30H48. The linear triterpene

squalene , the major constituent of shark liver oil, is

derived from the reductive coupling of two molecules of

farnesyl pyrophosphate.

Triterpenes



Squalene is then processed biosynthetically to generate either lanosterol or cycloartenol , the structural precursors to all the steroids.

farnesyl pyrophosphate



Ginsenosides are a class of triterpene saponins, found

exclusively in the plant genus Panax (ginseng).

Ginsenosides have been the target of research, as they

are viewed as the active compounds behind the claims

of ginseng's efficacy.



Ginsenoside Rb1

• most abundant in Panax quinquefolius (American Ginseng). • affect the reproductive system in animal testicles. • recent research ---- affects rat embryo development. • may increase testosterone production in male rats indirectly through the stimulation of the luteinizing hormone. • inhibits chemoinvasion and angiogenesis.



Ginsenoside Rc

is recognized for producing more sedative related

results than other ginsenosides



In one particular study on breast cancer and different

ginsenosides, it was found that only ginsenoside-Rc

was capable of inhibiting the growth of these cancer

cells. This suggests that there is a possibility that

ginsenoside-Rc may have effects that prevent or limit

the development of breast cancer.



• A further study was also able to demonstrate a

possible effect of ginsenoside-Rc on the motility of

sperm. Data from this experimentation showed a

significant increase in motility when the sperm was in a

ginsenoside-Rc solution.



Ginsenoside Rg1

• Most abundant in Panax ginseng (Chinese/Korean

Ginseng).

• Improves the capability of spatial learning for mice,

plus estrogen-like activity (which could account for the

boosting of "yin" theory)



Tetraterpenes and carotenoids

•Vitamin-A

• Physiologic importance

• Deficiency



Some biologically important compounds such as retinol,

retinal, and phytol. They are known to be antimicrobial

and antiinflammatory.



CH3

H3C CH3

H3CCH3 CH3

CH3 CH3

Β-carotene



Preparations… - Tretinoin - Isotretinoin



Thank you



terpenoids & volatile oils - wordpress.com origin of terpenoids 5 terpenoids & volatile oils...

Documents