Lipids
Anna Drew
with grateful acknowledgement for inspirational teaching received at
The School of Pharmacy, University of London
LIPIDS
• 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
• Lipids or ‘fatty esters’ are an important group
– long chain fatty acid + alcohols eg glycerol
Fixed oils & fats
• 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
• Mixed triglyceride
– fatty acid groups different
– more usual in nature
• 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
• 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
– eg peanut oil
– may contain essential fatty acids (linoleic acid, arachidonic acid
required in prostaglandin formation)
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
• world’s 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%
GS2U 52%
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 can’t 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
• 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)
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
• found in “vittae” in the outer layer is characteristic
• 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
• Water distillation
– wood chips in chamber and heated until water distills over
– crushed sample must be stable
• Cold expression
– citrus fruit oil (lemon, orange, bergamot)
– rasping process breaks oil sacs in rind
– pour cold water over and then separate oil and water
• Enfleurage
– petals (rose) placed between glass sheets covered in sheep or
pig fat
– oil seeps into fat and can be extracted with methanol
• Destructive distillation
– produces a different product from the one started with
– pine and juniper heated to exclude air over
• aqueous part - wood naphtha (ethanol and crude acetic acid) to
attract juniper oil
• non-aqueous part – resin (pine tar) to attract C5-C20 molecules
including monoterpenes
• like a fractional distillation
• Menthol and camphor
– nearly solid at room temperature
camphor
– can isolate by freezing oils out
– cheaper to synthesize camphor but generally extracted from
plants
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
• Clove
– Syzygium aromaticum
» eugenol 82%
» used on sore teeth to deaden pain
• Eucalyptus oil
» 1,8-cineole 70%
(sesquiterpene)
[3] Perfumes
• Rose oil
– Rosa gallica, R. damescena
» trans-geraneol
» and isomer cis-nerol
• Lavender oil
• Citrus oil
[4] Insect repellant, antimating device
• Citronella oil
– from grass
– doesn’t work well
[5] Starting materials
• Turpentine
– (for synthesis of other compounds)