26
Organic
Chemistry
William H. Brown &
Christopher S. Foote
26-1
26
Lipids
Chapter 26
26-2
26 Lipids
 Lipids:
a heterogeneous class of naturally
occurring organic compounds classified
together on the basis of common solubility
properties
• they are insoluble in water but soluble in aprotic
organic solvents, including diethyl ether, methylene
chloride, and acetone
 Lipids
include
• triglycerides, phospholipids, prostaglandins,
prostacyclins, and fat-soluble vitamins
• cholesterol, steroid hormones, and bile acids
26-3
26 Triglycerides
 Triglyceride:
an ester of glycerol with three fatty
acids
O
O CH2 OCR
R'COCH
1 . Na OH, H2 O
O
2 . HCl, H2 O
CH2 OCR' '
A triglyceride
CH2 OH
HOCH
+
CH2 OH
1,2,3-Propanetriol
(Glycerol, glycerin)
RCOOH
R' COOH
R' ' COOH
Fatty acids
26-4
26 Fatty Acids
 Fatty
acid: an unbranched chain carboxylic acid
derived from hydrolysis of animal fats, vegetable
oils, or membrane phospholipids
• nearly all have an even number of carbon atoms, most
between 12 and 20, in an unbranched chain
• the three most abundant are palmitic (16:0), stearic
acid (18:0), and oleic acid (18:1)
• in most unsaturated fatty acids, the cis isomer
predominates; the trans isomer is rare
• unsaturated fatty acids have lower melting points than
their saturated counterparts; the greater the degree of
unsaturation, the lower the melting point
26-5
26
Carbon Atoms/ Common
Double Bonds* Name
Melting Point
(°C)
Saturated Fatty Acids
12:0
Lauric acid
44
14:0
Myristic acid
58
16:0
Palmitic acid
63
18:0
Stearic acid
70
20:0
Arachidic acid
77
Unsaturated Fatty Acids
16:1
Palmitoleic acid
18:1
Oleic acid
16
18:2
Linoleic acid
-5
18:3
Linolenic acid
-11
20:4
Arachidonic acid -49
1
26-6
26 Triglycerides
 Physical
properties depend on the fatty acid
components
• melting point increases as the number of carbons in
its hydrocarbon chains increases and as the number
of double bonds decreases
• triglycerides rich in unsaturated fatty acids are
generally liquid at room temperature and are called
oils
• triglycerides rich in saturated fatty acids are generally
semisolids or solids at room temperature and are
called fats
26-7
26 Triglycerides
 The
lower melting points of triglycerides rich in
unsaturated fatty acids are related to differences
in their three-dimensional shape
• hydrocarbon chains of saturated fatty acids can lie
parallel with strong dispersion forces between their
chains; they pack into well-ordered, compact
crystalline forms and melt above room temperature
• because of the cis configuration of the double bonds
in unsaturated fatty acids, their hydrocarbon chains
have a less ordered structure and dispersion forces
between them are weaker; these triglycerides have
melting points below room temperature
26-8
26 Soaps and Detergents
 Natural
soaps are prepared by boiling lard or
other animal fat with NaOH, in a reaction called
saponification (Latin, sapo, soap)
O
O CH2 OCR
saponification
+
3
N
aOH
RCOCH
O
CH2 OCR
A triglyceride
(a triester of glycerol)
CH2 OH
CHOH
+
CH2 OH
1,2,3-Propanetriol
(Glycerol; Glycerin)
O
+
3 RCO N a
Sodium soaps
26-9
26 Soaps and Detergents
 Soaps
clean by acting as emulsifying agents
• their long hydrophobic hydrocarbon chains are
insoluble in water and tend to cluster in such a way as
to minimize their contact with water
• their polar hydrophilic carboxylate groups, on the
other hand, tend to remain in contact with the
surrounding water molecules
• driven by these two forces, soap molecules
spontaneously cluster into micelles
26-10
26 Soaps and Detergents
• micelle: a spherical arrangement of organic molecules
in water clustered so that their hydrophobic parts are
buried inside the sphere and their hydrophilic parts
are on the surface of the sphere and in contact with
water
• when soap is mixed with water-insoluble grease, oil,
and fats, the nonpolar parts of the soap micelles
“dissolve” these nonpolar dirt molecules and they are
carried away in the polar wash water
26-11
26 Soaps and Detergents
 Soaps
form water-insoluble salts when used in
water containing Ca(II), Mg(II), and Fe(III) ions
(hard water)
-
2 CH3 ( CH2 ) 1 4 COO Na
+ +
2+
Ca
A sodium soap
(soluble in water as micelles)
-
[ CH3 ( CH2 ) 1 4 COO ] 2 Ca
2+
+ 2 N a+
Calcium salt of a fatty acid
(insoluble in water)
26-12
26 Synthetic Detergents
 The
design criteria for a good detergent are
• a long hydrocarbon tail of 12 to 20 carbons
• a polar head group that does not form insoluble salts
with Ca(II), Mg(II), or Fe(III) ions
 The
most widely used synthetic detergents are
the linear alkylbenzenesulfonates (LAS)
26-13
26 Soaps and Detergents
1 . H2 SO 4
2 . Na OH
CH 3 ( CH2 ) 1 0 CH 2
Dodecylbenzene
CH 3 ( CH2 ) 1 0 CH 2
SO 3
-
Na
+
Sodium 4-dodecylbenzenesulfonate
(an anionic detergent)
 Also
added to detergent preparations are
• foam stabilizers
• bleaches
• optical brighteners
26-14
26 Prostaglandins
 Prostaglandins:
a family of compounds that
have the 20-carbon skeleton of prostanoic acid
9
5
7
1
3
8
6
4
2
12
14
16
18
COOH
10
11
13
15
17
19
20
Prostanoic acid
26-15
26 Prostaglandins
 Prostaglandins
are not stored in tissues as such,
but are synthesized from membrane-bound 20carbon polyunsaturated fatty acids in response
to specific physiological triggers
• one such polyunsaturated fatty acid is arachidonic
acid
9
8
11 12
6
14
5
COOH
15
Arachidonic acid
26-16
26 Prostaglandins
• among the prostaglandins synthesized biochemically
from arachidonic acid are
O
9
PGE 2
COOH
11
15
HO
HO H
HO
9
PGF 2
COOH
11
15
HO
HO H
26-17
26 Prostaglandins
 Research
on the involvement of PGs in
reproductive physiology has produced several
clinically useful derivatives
• 15-methyl-PGF2 is used as a therapeutic abortifacient
extra methyl group
at carbon-15
HO
9
COOH
11
15
HO
HO CH3
15-Methyl-PGF 2 
26-18
26 Prostaglandins
• the PGE1 analog, misoprostol, is used to prevent the
ulceration associated with the use of aspirin-like
NSAIDs
O
COOH
PGE 1
15
HO
16
HO H
O
COOCH 3
Misoprostol
HO
HO
15
CH3
16
26-19
26 Eicosanoids
 The
prostaglandins are members of an even
larger family of compounds called eicosanoids,
all of which contain 20 carbons and are derived
from polyunsaturated fatty acids
H
9
8
1
COOH
O
H
11
O
12
15
20
OH
Thromboxane A2
(a potent vasoconstrictor)
26-20
26 Eicosanoids
 Leukotrienes
are found primarily in white blood
cells. One function is constriction of smooth
muscles, especially those of the lungs
11
9
20
7
HO
6
1
COOH
5
S
O
14
L-cysteine
Leukotriene C4 (LTC4)
(a smooth muscle constrictor)
COOH
N
H
HN
glycine
COOH
N H2
L-glutamic acid
O
26-21
26 Steroids
 Steroids:
a group of plant and animal lipids that
have this tetracyclic ring structure
C
A
D
B
 The
features common to the ring system of most
naturally occurring steroids are illustrated on the
next screen
26-22
26 Steroids
• the fusion of rings is trans and each atom or group at
a ring junction is axial
• the pattern of atoms or groups along the ring
junctions is nearly always trans-anti-trans-anti-trans
• the steroid system is nearly flat and quite rigid
• most have have axial methyl groups at C-10 and C-13
CH3
H
H
CH3
H
H
26-23
26 Cholesterol
H3 C
H3 C
H
H
H
HO
26-24
26 Androgens
 Androgens
- male sex hormones
• synthesized in the testes
• responsible for the development of male secondary
sex characteristics
H3 C
H3 C
OH
H
H
H
O
H3 C
H3 C
H
O
H
H
H
HO
Testosterone
Androsterone
26-25
26 Anabolic Steroids
 Among
the synthetic anabolic steroids are
H3 C
H3 C
2
OH
H3 C OH
CH3
17
H
H3 C
CH3
H
1
H
H
HN
A
H
H
N
O
Methandrostenolone
H
Stanozolol
26-26
26 Estrogens
 Estrogens
- female sex hormones
• synthesized in the ovaries
• responsible for the development of female secondary
sex characteristics and control of the menstrual cycle
CH3
H3 C
H3 C C= O
H
H3 C
H
H
H
O
Progesterone
H
H
HO
O
H
Estrone
26-27
26 Synthetic Estrogens
 Progesterone-like
analogs are used in oral
contraceptives
"Nor" refers to the absence
of a methyl group here.
The methyl group is present
in ethindrone
HO
C CH
H3 C
H
H
H
H
O
Norethindrone
26-28
26 Glucorticoid Hormones
•
•
•
•
synthesized in the adrenal cortex
regulate metabolism of carbohydrates
decrease inflammation
involved in the reaction to stress
CH2 OH
H3 C
O
H3 C
C= O
OH
H
H
O
CH2 OH
H3 C
HO
H3 C
H
C= O
OH
H
H
H
O
Cortisone
Cortisol
26-29
26 Mineralocorticoid Horm.
• synthesized in the adrenal cortex
• regulate blood pressure and volume by stimulating
the kidneys to absorb Na+, Cl-, and HCO3OH
O
H3 C
C=O
H
H
O
CH
CH2 OH
H
Aldosterone
26-30
26 Bile Acids
 Synthesized
in the liver, stored in the
gallbladder, and secreted into the intestine
where their function is emulsify dietary fats and
aid in their absorption and digestion
OH
COOH
H
H
HO
H
H
OH
26-31
26 Biosynthesis of Steroids
 The
building block from which all carbon atoms
of steroids are derived is the two carbon acetyl
group of acetyl-CoA
Stage 1: synthesis of isopentenyl pyrophosphate from
three molecules of acetyl-CoA (Sect 19.4)
Stage 2: synthesis of cholesterol
Stage 3: conversion of cholesterol to other steroids
cholesterol
bile acids (e.g., cholic acid)
sex hormones (e.g., testosterone and estrone)
mineralocorticoid hormones (e.g., aldosterone)
glucocorticoid hormones (e.g., cortisone)
26-32
26
O HO CH3
O
CH3 -C- S- Co A
Acetyl Coenzyme A
-
O
OH
(R)-Mevalonate
OP2 O6 3 Isopentenyl pyrophosphate
C10 terpenes
( C1 0 ) Geranyl pyrophosphate
C15 and C20 terpenes
( C1 5 ) Farnesyl pyrophosphate
C30 terpenes
( C3 0 ) Squalene
Cholesterol
26-33
26 Phospholipids
 Phospholipids
are the second most abundant
group of naturally occurring lipids
• they are found almost exclusively in plant and animal
membranes, which typically consist of 40% -50%
phospholipids and 50% - 60% proteins
• the most abundant phospholipids are derived from
phosphatidic acid, a molecule in which glycerol is
esterified with two molecules of fatty acid and one of
phosphoric acid
• the three most abundant fatty acids in phosphatidic
acids are palmitic acid (16:0), stearic acid (18:0), and
oleic acid (18:1)
26-34
26 Phospholipids
A
phosphatidic acid
stearic acid
O
CH2 -O- P-O O
OO CH
O CH2
palmitic acid
O
glycerol
• further esterification with a low-molecular weight
alcohol gives a phospholipid
• among the most common of these low-molecularweight alcohols are
26-35
26 Phospholipids
• among the most common of these low-molecularweight alcohols are
HOCH2 CH 2 NH 2
Ethanolamine
+
HOCH2 CH 2 N( CH3 ) 3
Phosphatidylethanolamine
(Cephalin)
Choline
Phosphatidylcholine
(Lecithin)
Serine
Phosphatidylserine
HOCH2 CH COO
N H3
HO
HO
-
+
OH
HO
OH
OH Inositol
Phosphatidylinositol
26-36
26 Phospholipids
A
lecithin
stearic acid
O
choline
O
+
O P OCH2 CH2 N( CH 3 ) 3
OCH2
O CH
O CH2
palmitic acid
glycerol
O
in aqueous solution, phospholipids spontaneously
form into a lipid bilayer, with a back-to-back
arrangement of lipid monolayers
26-37
26 Biological Membranes
 Fluid
mosaic model: a biological membrane
consists of a phospholipid bilayer with proteins,
carbohydrates, and other lipids embedded on
the surface and in the bilayer
• fluid signifies that the protein components of
membranes “float” in the bilayer and can move freely
along the plane of the membrane
• mosaic signifies that the various components of the
membrane exist side by side, as discrete units rather
than combining to form new molecules and ions
26-38
26 Fat-Soluble Vitamins
 Vitamins
are divided into two broad classes on
the basis of their solubility
• those that are fat soluble, and hence classified as
lipids
• those that are water soluble
 The
fat-soluble vitamins include A, D, E, and K
26-39
26 Vitamin A
• occurs only in the animal world
• found in the plant world in the form of a provitamin in
a group of pigments called carotenes
cleavage of this
C=C gives vitamin A
-Carotene
enzyme-catalyzed cleavage
and reduction in the liver
CH2 OH
2
Retinol (Vitamin A)
26-40
26 Vitamin A
 The
best understood role of Vitamin A is its
participation in the visual cycle in rod cells
• the active molecule is retinal (vitamin A aldehyde),
which forms an imine with an -NH2 group of the
protein opsin to form the visual pigment called
rhodopsin
• the primary chemical event of vision in rod cells is
absorption of light by rhodopsin followed by
isomerization of the 11-cis double bond to the 11-trans
configuration
26-41
26 Vitamin A
11
12
CH= N -op sin
light
11
CH= N -op sin
12
26-42
26 Vitamin D
A
group of structurally related compounds that
play a role in the regulation of calcium and
phosphorus metabolism
• the most abundant form in the circulatory system is
vitamin D3
HO
Vitamin D 3
26-43
26 Vitamin E
 Vitamin
E is a group of compounds of similar
structure, the most active of which is tocopherol
Four isoprene units, joined
OH
head-to-tail, beginning here
and ending at the aromatic ring
O
Vitamin E (-Tocopherol)
• In the body, vitamin E functions as an antioxidant; it
traps peroxy radicals of the type HOO• and ROO•
formed as a result of oxidation by O2 of unsaturated
hydrocarbon chains in membrane phospholipids
26-44
26 Vitamin K
 The
name of this vitamin comes from the
German word Koagulation, signifying its
important role in the blood-clotting process
O
isoprene units
O
Vitamin K 1
2
O
O
Menadione
(a synthetic
vitamin K analog)
26-45
26 Prob 26.12
Account for the detergent properties of each compound.
(a)
CH3 Cl +
CH3 ( CH2 ) 6 CH2 N CH 3
CH2 C6 H5
Benzyldimethyloctylammonium chloride
(a cationic detergent)
HOCH2
O
(b) HOCH2 CCH2 OC( CH 2 ) 1 4 CH3
HOCH2
Pentaerythrityl palmitate
(a neutral detergent)
26-46
26 Prob 26.15
Palmitic acid, CH3(CH2)14COOH, is used to prepare the
hydrocarbon portions of these surface-acting germicides
and fungicides. Show how to convert palmitic acid to 1chlorohexadecane (cetyl chloride), and to N,Ndimethylhexadecanamine.
N+
Cl
-
CH2 ( CH2 ) 1 4 CH3
Cetylpyridinium chloride
Cl
-
CH3
+
CH2 N CH2 ( CH 2 ) 1 4 CH3
CH3
Benzylcetyldimethylammonium chloride
26-47
26 Prob 26.16
Calculate the number of grams of epoxyalcohol that can
be obtained from 100 g of racemic epoxyester by this
stereospecific enzyme-catalyzed hydrolysis.
O
O
H2 O, OH lipase
O
A racemic mixture
O
O
O
H
This enantiomer
is recovered
unhydrolyzed
O
+ O
OH +
-
O
H
This epoxyalcohol
is obtained in
pure form
26-48
26 Prob 26.18
Compare the structural formulas of unoprostone and
PGF2.
HO
HO
COOH
CH3
Unoprostone
(antiglaucoma)
COOH
PGF 2 
Stimulates contraction of
uterine smooth muscle.
O
HO
HO
HO H
26-49
26 Prob 26.19
On this and the next two screens are the steps in the
laboratory synthesis of doxaprost, an orally active
bronchodilator. Propose reagents to bring about each
step. Note that the bottom reactions on each screen are
repeated at the top of the following screen.
O
O
COOEt
( CH 2 ) 6 COOCH 3
(1)
O
(2)
O
COOH
( CH2 ) 6 COOH
COOEt
( CH2 ) 6 COOH
(3)
(4)
26-50
26 Prob 26.19 (cont’d)
• Doxoprost (reactions 3 and 4 are repeated here)
O
O
COOH
( CH2 ) 6 COOH
( CH2 ) 6 COOH
O
(3)
(4)
O
Br
( CH2 ) 6 COOH
( CH2 ) 6 COOH
(5)
(6)
O
O
( CH2 ) 6 COOCH3
( CH2 ) 6 COOCH3
(7)
Nef
reaction
(8)
CH2 N O 2
26-51
26 Prob 26.19 (cont’d)
• Doxoprost
O
O
( CH 2 ) 6 COOCH 3
( CH 2 ) 6 COOCH3
Nef
reaction
(7)
(8)
CH2 N O 2
O
O
( CH 2 ) 6 COOCH3
(9)
C= O
H
( CH 2 ) 6 COOCH3
H
C
( CH 2 ) 4 CH 3
C
C
H
O
(10)
O
O
C
H
( CH 2 ) 6 COOH
H
C C ( CH2 ) 4 CH 3
O
(11)
( CH 2 ) 6 COOH
H
( CH 2 ) 4 CH 3
C C C
H HO CH 3
26-52
26 Prob 26.24
Draw a stereorepresentation of cortisol showing the
conformation of the five-membered ring and each sixmembered ring.
CH2 OH
H3 C C= O
OH
HO
H3 C
H
H
Cortisol
(Hydrocortisone)
H
O
26-53
26 Prob 26.25
Knowing what you do about the requirement for transcoplanar ring opening of epoxide rings, draw the
structural formula of the product formed by treating each
epoxide with LiAlH4.
CH3
CH 3
O H3 C
(a)
O H3 C
H
H
(b)
H
H
H
H
CH3
H3 C
(c)
O
CH 3
H3 C
H
H
H
(d)
O
H
H
H
26-54
26 Prob 26.31
State the number of cis,trans isomers possible for
vitamin A.
CH2 OH
Retinol
(Vitamin A)
26-55
26
Lipids
End Chapter 26
26-56