Lipids

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Lipids

• Anna Drew
• with grateful acknowledgement for inspirational
  teaching received at
• The School of Pharmacy, University of London

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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

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Fixed oils fats

• Esters of glycerol
• 3 fatty acids may be involved gt triglyceride
  (main component of oils and fats)
• some may exist as free acids
• Fish oils may have 12 fatty acids which vary

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• Simple triglyceride (triacylglycerol)
• all fatty acid groups the same
• Mixed triglyceride
• fatty acid groups different
• more usual in nature

-gt yields 3 molecules of palmatic acid
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• Saturated or unsaturated
• unsaturated acids oleic, linoleic, linolenic,
  palmitolinic
• saturated acids palmitic, myristic, stearic
• Fatty acid content determines properties
• large amount of saturated -gt solid at room temp.
• large amount of unsaturated -gt liquid at room
  temp.

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• 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 -gt rancid oil
  (depending on degree of saturation)
• leave a permanent grease stain on filter paper

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• 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

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Chemical tests

• solubility
• freezing point, melting point
• refractive index (and sometimes optical rotation)
• density
• volatile acidity, unsaponifiable matter, acetyl
  value

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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

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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)

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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

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• 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)

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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

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• 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 gt710C
• used as a test for adulteration of olive oil

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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)

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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

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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

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

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• 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

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• 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

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Extraction

• enzymes in cells can break down oils in cells
• some oils highly unsaturated and easily oxidized
  heat in air gt rapid oxidation
• 1 Cold expression
• 2 Steam treatment expression
• 3 Solvent extraction

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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

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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 proteinfibre fed to animals
  once ricin removed

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• 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

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• 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

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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

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• 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

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Monoterpene components

• Hydrocarbons
• Alcohols

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• Aldehydes
• all produced via the terpenoid pathway
• Ketones

Citral
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• Esters
• Oxides

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Sesquiterpenes (C15)

• Hydrocarbons Phenols Phenolic
  esters

Anethole
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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

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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

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• 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

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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

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• 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
• can isolate by freezing oils out
• cheaper to synthesize camphor but generally
  extracted from plants

camphor
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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

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• 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)

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• 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)
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• 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
• doesnt work well
• 5 Starting materials