PHARM.

D Chemical Pharmacognosy- I Lecture 33 May 25th, 2011

LIPIDS INTRODUCTION
M. Ahsan Khalid, B.Pharm, Pharm. D B.Pharm,
M.Phil Scholar (RIPS/RIU) HIPSHIPS-HUKIC

LIPIDS
Lipids are a broad group of naturally occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The main biological functions of lipids include energy storage, as structural components of cell membranes, and as important signaling molecules.

Simple: fixed oils, fats, waxes Complex: Phosphatides, lecithins

may contain P, N as well as C, H, O

widely distributed in plant and animal kingdom

in all living cells sometimes accumulate to be commercially useful
plants - food reserve (fruit and seeds) animals insulation, energy sources, protection

Fixed oils & fats

Any substance that is liquid at ambient temperatures and is hydrophobic but soluble in organic solvents. Oils have a high carbon and hydrogen content and are nonpolar substances.

Esters of glycerol:
3 fatty acids may be involved => triglyceride (main component of oils and fats) some may exist as free acids [Fish oils may have 12 fatty acids which vary]

 Simple triglyceride (triacylglycerol)

all fatty acid groups the same

-> yields 3 molecules of palmatic acid

 Saturated or unsaturated:

unsaturated acids: oleic, linoleic, linolenic, palmitolinic saturated acids: palmitic, myristic, stearic

Fatty acid content determines properties

large amount of saturated -> solid at room temp. large amount of unsaturated -> liquid at room temp.

 most vegetable products contain a high number of triglycerides with unsaturated fatty acids liquid most animal products opposite where large number of unsaturated fatty acids readily oxidizes eg whale, fish oils, linseed

Expect a good (fixed) oil to be:

odourless, tastleless and non-volatile soluble in a lipid solvent fairly readily air-oxidized -> rancid oil (depending on degree of saturation) leave a permanent grease stain on filter paper

 Determination of structure
By hydrolysis or saponification in 2 ways:
i) Alkaline hydrolysis with KOH
splits triacylglycerol into parent glycerol and releases all fatty acids arrangement of fatty acids is unknown

ii) Can use an enzyme (pancreatic lipase)

hydrolyses two outer glycerides and then remove final group with KOH

Detecting fatty acids

GLC not volatile so have to form a methylether and separate them by chain length

Chemical tests
solubility freezing point, melting point refractive index (and sometimes optical rotation) density

volatile acidity, unsaponifiable matter, acetyl value

Waxes
Wax refers to a class of chemical compounds that are plastic near ambient temperatures. Characteristically, they melt above 45 C (113 F) to give a low viscosity liquid. Waxes are insoluble in water but soluble in organic, nonpolar solvents

Waxes
contain appreciable quantities of
esters derived from higher monohydric alcohols (one OH group) of the methyl (1y) alcohol series combined with fatty acids (C16 C32)

Most are solids at room temperature

can only be saponified by alcoholic alkali often contain free acids, hydrocarbons, free alcohols and sterols saponification and acid values higher, iodine values lower

Commercially important examples

Vegetable: carnuba Animal: spermaceti, beeswax, wool fat

Uses
Readily absorbed through skin
ointments

Protect from entry of water

eg cod liver oil, linseed oil

Vehicles for injections Waxes in enteric coatings Pharmacological substances

vitamin A and D in cod liver oil

Food source
E.g peanut oil may contain essential fatty acids (linoleic acid, arachidonic acid required in prostaglandin formation)

EXAMPLES: Olive oil

salad oil, sweet oil From ripe fruits of Oleo europoea (Oleaceae)
Mediterranean, California native of Palestine, known in Egypt in 7th century B.C., introduced into Spain early on

pale yellow with greenish tinge (chlorophyll and carotene) bland, slight odour, goes pasty/cloudy at 10oC

 tested for absence of arachis oil, cotton-seed oil, sesame oil, peanut oil and tea-seed oil (Camellia sasanqua) Composition:

high iodine value, low acid value Uses

salad oil, soaps, plasters manufacture of parenteral preparations (low acid value, free of water)

Arachis oil
From seeds of Arachis hypogaea (Leguminosae) groundnut cultivated in tropical Africa, India, Brazil, southern USA and Australia worlds 4th largest source of a fixed oil seeds contain 40-50% oil fruits shelled by a machine kernels difficult to express; crushed and cooked at low pressure seed cake fed to cattle

 Composition:
oleic acid ~ 60% linoleic acid 24% palmitic acid 9% arachidonic acid

GU3, GSU2 like olive oil

acid and saponification values similar to olive oil if fatty acids are separated (hydrolysis) the presence of arachidonic acid gives a melting point >710C
used as a test for adulteration of olive oil

Castor oil
From seeds of Ricinus communis (Euphorbiaceae) India, Africa, Europe Contains ricinoleic acid 91%, glycerides GU3
must be free of ricin

pale yellow, very viscous, acrid tasting soluble in ethanol (unlike most oils) due to so much hydroxy- acid Used in toothpaste, nail varnish remover, lubricant industry and pharmacy (as derivatives)

Almond oil
From Prunus amygdalus v. amara (bitter used in pharmacy), v. dulcis (sweet) native to Far East, grown in Mediterranean, N.California Oil is highly unsaturated
with oleic acid 77%, linoleic acid 17% 83% GU3, 17% GSU2

Bitter almond oil also contains amygdalin (glycoside) which decomposes to benazldehyde + HCN Used in pharmacy in oily injections and ointments
prone to oxidation so has to be kept air-free or goes rancid transfer to smaller bottle to exclude air

Theobroma oil
Cocoa butter From seeds of Theobroma cacao (Sterculaceaea) Central America, also cultivated in Brazil, W.Africa (Nigeria) Solid oil
high steric and palmitic acid content (35%, 25%), oleic acid 3% melting point 31-350C low iodine value because saturated most expensive commercial fixed oil (adulterated)

Mainly used in suppositories

Animal products
Cod and Halibut liver oils
mixed triglycerides, mainly unsaturated C16-22 acids and decahexanoic acid Used for Vitamin A and D content (halibut > cod)

Beeswax
yellow and white from honeycomb simple esters of 1y alcohols with a high degree of myricyl palmitate (80%) (C15H31OOC30H61) ester:acid ratio value 3.3-4.2 Used in paraffin ointment, plasters and enteric coating

 Carnuba wax
an adulterate of beeswax From the cuticle of the South American palm Copenicia cerifera Used in tablet coatings

Spermaceti
From the head of sperm (Physeter macrocephalus) and bottle-nosed whales (Hyperodon rostratus) just above right nostril) 500lb from 1 whale simple esters of cetyl alcohol CH3(CH2)4CH2OH cetyl palmitate, cetyl myistate 90-93% no longer used pharmaceutically, can be replaced by jojoba oil

 Wool fat
From the wool of sheep (Ovis aries) Complex composition:
esters of cholesteryl and isocholesteryl + estolidic 32-33% esters of normal aliphatic alcohols with fatty acids 48-49%

Used as an emollient base for creams and ointments

major component of most ointments melting point 30-42oC readily absorbed through skin absorbs twice its own weight in water so makes an emulsion

Extraction
enzymes in cells can break down oils in cells some oils highly unsaturated and easily oxidized heat in air > rapid oxidation [1] Cold expression [2] Steam treatment + expression [3] Solvent extraction

[1] Cold method

Castor beans
roll to break down testa winnow to separate seed coat from seed

Olives
put into press light pressure applied gives the 1st grade oil used in pharmacy oil washed to remove pigment floats to the top and is skimmed off 30-40% oil recovered not economical

[2] Steam treatment + expression

material left over from [1] undergoes steam treatment
repressed to get 2nd fraction of oil

[3] Solvent extraction

to get 100% of oil out last portion gives a low grade used to industrial paints etc left with high protein+fibre fed to animals once ricin removed

 Cocoa seeds
fat is solid so cant cold express use hot expression with steam treatment oil is a byproduct of the cocoa industry

Cod liver and halibut

livers heated by steam process in an inert atmosphere mixture separated by centrifugation oil dried in drying towers gives a clear bright highly refined oil cooled to 0oC to remove saturated stearic fats leaves polyunsaturated triglycerides standardised for vitamin content stored in airtight containers in the dark

 Spermacetin
ensure well separated from normal triglycerides washed with alkali

Wool fat
has to be cleaned up acidified to precipitate waxes free fatty acids removed by forming salts wax extracted with acetate product can be bleached to give light yellow colour or left as dark yellow wax

Volatile oils
A concentrated hydrophobic liquid containing volatile aroma compounds from plants. Essential oils are also known as volatile oils, ethereal oils or aetherolea, or simply as the "oil of" the plant from which they were extracted, such as oil of clove. An oil is "essential" in the sense that it carries a distinctive scent, or essence, of the plant.

Volatile oils
different from fixed components of plants that are
highly odiferous generally occur as they are secreted in oil cells in specialised structures
ducts, cavities, glandular hairs

frequently associated with other substances

gums, resins (resinify on exposure to air)

mainly terpenoid
some phenol ethers and phenols

 Terpenoids
based on the 5C isoprene unit

Monoterpenes
most important, most volatile
di-, tri-, sesquiterpenes also important

contain 2 condensed 5C units head-tail most formed from geranyl pyrophosphate

Monoterpene components
Hydrocarbons

Alcohols

 Aldehydes
Citral

all produced via the terpenoid pathway

Ketones

 Esters

Oxides

Sesquiterpenes (C15)
Class of terpenes that consist of three isoprene units

Hydrocarbons

Phenols

Phenolic esters

Anethole

Chemical and physical properties

volatile liquids with no colour
keep in amber bottles with minimum air

odour asymetric centres, isomers with optical activity

only one isomer occurs naturally

refractive index normally high

is a means to characterise the oil

miscible in water and soluble in organic solvents

more soluble if contains OH fatty acids

reasonably heat stable

can be steam distilled

tend to be used as solvents for resins

Families
Economically only a few family groups are commercially useful [1] Labiatae
Lavender, Mentha Sp.
large number, tend to hybridise oil occurs in special organs
synthesized in glandular trichomes (mint)

burst easily releasing oil

[2] Umbelliferae
Fruits (best if ripe): anise, caraway, fennel, coriander
steam distill to remove oils

[3] Pinaceae
Pine, juniper
found in resin ducts in outer old xylem or bark released when bark removed

[4] Rutaceae
Citrus fruits
typical ductless sacs in outer part of fruit rind found at various depths before albino layer (white bitter pithy part) oil is there under pressure and will burst open when rasped less stable, need more care

[5] Lauraceae
Cinnamon, camphor
from region immediately below bark

Method of extraction
Depends where oils lies and its stability Steam distillation
gentle, herb + water heated and oil distilled over
Raw plant material, consisting of the flowers, leaves, wood, bark, roots, seeds, or peel, is put into distillation apparatus over water. As the water is heated, the steam passes through the plant material, vaporizing the volatile compounds.

Water distillation

wood chips in chamber and heated until The vapors flow through a coil, water distills over where they condense back to liquid, which is then collected in crushed sample must be stable
the receiving vessel.

Cold expression
Most citrus peel oils are expressed mechanically, or cold pressed (similar to olive oil extraction). Due to the relatively large quantities of oil in citrus peel and low cost to grow and harvest the raw materials, citrus-fruit oils are cheaper than most other essential oils.

Solvent extraction
Most flowers contain too little volatile oil to undergo expression and their chemical components are too delicate and easily denatured by the high heat used in steam distillation. Instead, a solvent such as hexane or supercritical carbon dioxide is used to extract the oils. Extracts from hexane and other hydrophobic solvent are called concretes, which are a mixture of essential oil, waxes, resins, and other lipophilic (oil soluble) plant material.

Uses
as inhalations, orally, gargles, mouthwashes, trans-dermally

[1] Flavours & carminatives

Labiatae
Mentha piperita (peppermint oil)
50-75% menthol, also contains menthone etc used mainly in toothpastes

Mentha spicata (spearmint oil)

50-75% L-carvone some minor components similar to peppermint but major components differ giving different smell and taste

Lavendura officinalis (lavender oil)

35-45% linalyl acetate, also geraniol, limonene, cineole some varieties have a lower % so other compound characteristics dominate growing environment will affect quality

 Rutaceae
Citrus oils
D-limonene 90%, citral 4% + esters, pinene, d-limonene (small amount) high proportion of limonene desirable but a lot is removed after isolation by distillation under reduced pressure leaves oil high in citral which deteriorates on storage giving a turpentine odour

Citrus flower oils

no citral, other constituents that give a different odour and flavour of orange flower oil used in confectionary

Umbelliferae
Pimpinella anisum (anise), Foeniculum vulgare (fennel)
90% anethole some fennel variaties contain fenchone giving a bitter taste

Carum carvi (carraway)

carvone

Coriandum sativum (coriander)

60-80% linalool

[2] Local stimulants and antiseptics

(containing phenols)
Pinaceae
Pinus paulastrus destructive distillation phenol p-cresol Juniperus oxycedrus cadenine

(sesquiterpene)

Clove
Syzygium aromaticum eugenol 82% used on sore teeth to deaden pain

Eucalyptus oil
1,8-cineole 70%

[3] Perfumes
Rose oil
Rosa gallica, R. damescena trans-geraneol and isomer cis-nerol

Lavender oil Citrus oil

[4] Insect repellant

Citronella oil
from grass

[5] Starting materials

Turpentine
(for synthesis of other compounds)