Lipids

From
Organic Chemistry, Sixth Edition
Janice Gorzynski Smith
University of Hawai’i

1
 Lipids
Lipids are soluble in organic solvents but not water.
• They are identified based on a physical property and not by
the presence of a particular functional group.

All lipids have many C-C and C-H bonds but no common
functional groups to all lipids.

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 Hydrolyzability of Lipids
• Hydrolyzable lipids usually contain some kinds of ester groups.

• Non-hydrolyzable lipids usually contain no ester group.

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 Saturated fatty acids
Melting point
(oC)
lauric acid
dodecanoic acid CH3(CH2)10CO2H 44

myristic acid
tetradecanoic acid CH3(CH2)12CO2H 58

palmitic acid
hexadecanoic acid CH3(CH2)14CO2H 63

stearic acid
octadecanoic acid CH3(CH2)16CO2H 71

arachidic acid
eicosanoic acid CH3(CH2)18CO2H 73 4
 Unsaturated fatty acids
Melting point
(oC)
oleic acid
(9Z)-octadec-9-enoic acid 13

linoleic acid
(9Z,12Z)-octadeca-9,12-dienoic acid -5

linolenic acid
(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid -11

arachidonic acid
(5Z,8Z,11Z,14Z)-eicosa-5,8,11,14-tetraenoic acid -50
5
 Problem 1
Draw the structures of linoleic acid, linolenic acid and arachidonic
acid.

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 Waxes
Waxes are esters (RCOOR′) formed from a fatty acid (RCOOH)
and a high molecular weight alcohol (R′OH).
• Lanolin is a wax coating wool fibers of sheep. It is composed
of a complex mixture of 8,000-20,000 lanolin esters, resulting
from combinations between ~200 lanolin acids and ~100
lanolin alcohols.
• Spermaceti wax is isolated from the heads of sperm whales.
The main component is CH3(CH2)14COO(CH2)15CH3.

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 Triacylglycerols (triglycerides)
A triacylglycerols is an ester derived from glycerol and three fatty
acids.

It usually contain two or three different fatty acids. If three fatty

acids are identical, it is called homotriacylglycerol such as
palmitin and stearin.
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 Fats vs Oils
• Both fats and oils are triacylglycerols.
• A fats is solid but an oil is liquid at room temperature.
• The melting point of fats and oils correlates with the number of
degrees of unsaturation present in the fatty acid parts.
• Vegetable oils have higher percentage of unsaturated fatty
acids than animal fats.

Saturated triacylglycerol Unsaturated triacylglycerol

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 Fatty acid composition of
some fats and oils
Source %Saturated fatty acids %Oleic acid %Linoleic acid
Lard 39 45
Beef 49-62 37-43 2-3
Cow milk 37 33 3
Safflower 9 13 78
Corn 11-16 19-49 34-62
Olive 11 84 4
Soybean 15 20 52
Rice bran 25 38 34
Palm 43 40 8
Coconut 86 7 −

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 Problem 2
Some fish oils are rich in polyunsaturated triacylglycerols
consisting omega-3 fatty acids. What are omega-3 fatty acids?
Give an example of omega-3 fatty acid (name and structure).

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 Hydrolysis of Triacylglycerols

Saponification

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 Micelle formation of soap molecules
Hydrophilic head

Hydrophobic tail
Soap molecule is amphiphilic
13
 Problem 3
Draw the structure of molecular assembly in a soap
bubble.

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 Hydrogenation and Oxidation of
Triacylglycerols

Industrially used for preparation of

margarine from oil

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Causing some rancid oils 15
 Phospholipids
• Two common types of phospholipids: glycerophospholipids and
sphingomyelin.
• Phospholipids are phosphoric acid diester or phosphodiester.
• In cells, the phosphodiester has a net negative charge.

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 Glycerophospholipids
Glycerophospholipids = Phosphoglycerides = Phosphoacylglycerols

derived from fatty acids

derived from X-OH

(water or alcohol)

Glycerophospholipids are principal component of most cell membranes

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Examples of glycerophospholipids

glycerophospholipid

18
 Chirality of glycerophospholipids
The middle carbon of the glycerol backbone is a
stereogenic center, usually with the R configuration.
3 3

1 1

2 2

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 Problem 4
Draw the structure of phosphatidylserine with R
configuration at the glycerol backbone.

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 Micelle vs lipid bilayers

Soap Glycerophospholipid

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 Molecular self assembly of amphiphilic molecules
Critical packing parameter: CPP =V/(a0lc) Example

Surfactants
in water

Phospholipids
in water

Amphiphilic
molecules
in nonpolar
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 Sphingomyelin
• Sphingomyelin is an important class of sphingolipids containing
an amino alcohol with unsaturated C18 chain called sphingosine.

18 C chain

• Sphingomyelins have phosphodiester and amide groups.

Sphingomyelins are found in the myelin sheath, coating and

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insulating nerve cells. 23
 Examples of sphingolipids

Sphingosine Ceramide Sphingomyelin Sphingomyelin Cereboroside

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 Problem 5
• Draw general structures of triacylglycerol,
glycerophospholipid and sphingomyelin.

triacylglycerol glycerophospholipid sphingomyelin

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 Problem 6
• Answer the following questions based on the
structures of sphingosine, ceramides, sphingomyelins,
cerebrosides.
a) Which are phospholipids?
b) Which are nonhydrolizable lipids?

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 Nonhydrolyzable lipids

Although fat soluble vitamins must be

obtained in the diet, they do not have
to be consumed every day. Excess
vitamins are stored in fat cells, and
then
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 Vitamins E and K

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 Problem 7
Which fat soluble vitamins (A, D, E and K) are chiral
molecules? Assign the absolute configuration (R or S)
for each chiral carbon atom in the structures of those
vitamins?

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 Eicosanoids
• The eicosanoids are a group of potent biologically active compounds
derived from (5Z,8Z,11Z,14Z)-eicosa-5,8,11,14-tetraenoic acid or
arachidonic acid.

Examples:
• PGE1
• TXA2
• LTB4
• PGI2
• LTE4

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 Pharmaceutical relevance of eicosanoids

• Inhibition of COX-1 or COX-2, in the synthesis pathway of

eicosanoid, is the hallmark of NSAIDs (non-steroidal anti-
inflammatory drugs), such as aspirin.
• Prostanoids are known to mediate local symptoms of
inflammation: vasoconstriction or vasodilation, coagulation,
pain, and fever.
• Prostanoids activate the PPARγ hormone receptors, and
directly influence gene transcription.
• Prostanoids including their more stable analogs and their
receptor antagonists have many other relevancies to
clinical medicines.

https://en.wikipedia.org/wiki/Eicosanoid#Abbreviation
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 Terpenes
• Terpenes are lipids composed of isoprene units.
• An isoprene unit has 5 carbons
• Terpenes can be cyclic or acyclic, and may contain
heteroatoms.
Examples of terpenes

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 Classification of terpenes

Polyterpene 9-30,000 >40 Rubber

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 Problem 8

• Classify each of the following terpenes.

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 Biosynthesis of terpene
• Terpenes are synthesized from 2 pyroposphate (or
diphosphate) compounds i.e. isopentenyl pyrophosphate and
dimethylallyl pyrophosphate.
• Pyrophosphate (PPi) is a good leaving group.

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 Problem 9
Draw a mechanism for terpene formation which involve
both SN1 and E1 processes.

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 Squalene biosynthesis
A formation of
squalene, a
triterpene, involves a
two-stepped
reductive
dimerization of two
molecules of farnesyl
pyrophosphate.

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 Reactions of terpene pyrophosphates

hydrolysis

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 Problem 10
• Natural limonene found in citrus fruit peels is an (R)
isomer. Draw the structure of this compound showing
its stereochemistry.

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 Steroids
• Steroids are a group of tetracyclic lipids, many of which have
biological activity.
• Steroids are composed of 3 six-membered rings and 1 five-
membered ring.
• The rings are lettered A, B, C, and D, and the carbons are
numbered as shown.
• Many steroids also have methyl groups at the two-ring junctions
labeled as C18 and C19 and called angular methyl groups.

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 3D Structure of steroids
• In steroids, the trans ring fusion are more common.
• All methyl and H are oriented in axial position and opposite to
each other.

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 Cholesterol
• Cholesterol has 8 stereogenic carbons, so there are
28 = 256 possible stereoisomers.
• In nature, however, only the following stereoisomer exists:

• Cholesterol is an important component in cell membranes and

is the starting material for all other important steroids.
• Humans do not have to ingest cholesterol because it is
synthesized in the liver from squalene.
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 Biosynthesis of cholesterol

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 Cholesterol-lowering drugs
• Several available drugs can block the biosynthesis of
cholesterol and reduce the level of cholesterol in blood.
• Two examples are atorvastatin (Lipitor) and simvastatin (Zocor).

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 Steroidal sex hormones
Estradiol and estrone are estrogens, the
female sex hormones produced in the ovaries.
They are responsible for the development and
regulation of the female reproductive system
and secondary sex characteristics.

Progesterone is the pregnancy hormone. It is

responsible for the preparation of the uterus for
implantation of a fertilized egg.

Testosterone and androsterone are male sex

hormone synthesized in the testes, They are
responsible for the development of male
reproductive tissues such as testes and
prostate, as well as promoting secondary
sexual characteristics
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 Adrenal cortical steroids
• Adrenal cortical steroids e.g. cortisone, cortisol, and
aldosterone are synthesized in the outer layer of the adrenal
gland.
• Cortisone and cortisol serve as anti-inflammatory agents and
they also regulate carbohydrate metabolism.
• Aldosterone regulates blood pressure and volume by controlling
the concentration of Na+ and K+ in body fluids.

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 Synthetic hormone steroids
• Synthetic analogues of these steroids have found important uses, such as in
oral contraceptives.

• Synthetic male hormone analogues, called anabolic steroids, promote

muscle growth.
• Although they are used by athletes, their use is not permitted in competitive
sports.

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 Problem 11
From the structures of vitamin A, D, E and K, which
vitamin is most likely to be derived from cholesterol?

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