17
Introduction to Organic Chemistry
2 ed William H. Brown
17-1
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17
Lipids
Chapter 17
17-2
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Lipids: a heterogeneous class of naturally occurring organic compounds classified together on the basis of common solubility properties
insoluble in water soluble in aprotic organic solvents including diethyl ether, methylene chloride, and acetone
17 Lipids
Lipids include
triglycerides, phospholipids, prostaglandins, and fatsoluble vitamins cholesterol, steroid hormones, and bile acids
17-3
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Triglyceride: an ester of glycerol with three fatty acids O
O CH2 O- CR O R'CO- CH 1 . Na OH, H2 O 2 . HCl, H2 O CH2 OH HOCH + CH2 OH 1,2,3-Propanetriol (Glycerol, glycerin)
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Triglycerides
CH2 O- CR'' A triacylglycerol (a triglyceride)
RCO2 H R'CO2 H R''CO2 H Fatty acids
17-4
Fatty acid: a long, unbranched chain carboxylic acid, most commonly of 12 - 20 carbons, derived from hydrolysis of animal fats, vegetable oils, or the phospholipids of biological membranes In the shorthand notation for fatty acids
the number of carbons and the number of double bonds in the chain are shown by two numbers, separated by a colon
17 Fatty Acids
17-5
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Fatty Acids
Carbon Atoms/ Double Bonds 12:0 14:0 16:0 18:0 20:0 16:1 18:1 18:2 18:3 20:4 Common Name lauric acid myristic acid palmitic acid stearic acid arachidic acid palmitoleic acid oleic acid linoleic acid linolenic acid arachidonic acid mp (C) 44 58 63 70 77 1 16 -5 -11 -49
17-6
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Unsaturated
Saturated
Among the fatty acids most abundant in plants and animals
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
17-7
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Fatty Acids
Stearic and linolenic acids
17 Fatty Acids
17-8
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Physical properties of triglycerides depend on their fatty acid components
melting point increases as the number of carbons in their 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
17 Triglycerides
The lower melting points of triglycerides rich in unsaturated fatty acids are related to differences in their three-dimensional shape 17-9
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
A saturated triglyceride
17 Triglycerides
17-10
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Triglycerides rich in saturated fatty acids:
saturated hydrocarbon chains can lie parallel and there are strong dispersion forces between their chains they pack into well-ordered, compact crystalline forms and have melting points above room temperature
17 Triglycerides
Triglycerides rich in saturated fatty acids:
because of the cis configuration of their double bonds, their hydrocarbon chains have a less ordered structure dispersion forces between hydrocarbon chains are weaker; these triglycerides have melting points below room temperature
17-11
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Natural soaps are prepared by boiling lard or other animal fat with NaOH, in a reaction called saponification (Latin, sapo, soap)
O O CH2 O- CR
+
17 Soaps and Detergents
RCO- CH
3 Na OH
saponification CH 2 OH CHOH
+
O O 3 RCO Na Sodium soaps
+
CH2 O- CR A triacylglycerol (a triglyceride)
CH 2 OH 1,2,3-Propanetriol (Glycerol; Glycerin)
17-12
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Soaps clean by acting as emulsifying agents
the long hydrophobic hydrocarbon chains of soaps are insoluble in water and tend to cluster in such a way as to minimize their contact with water the polar hydrophilic carboxylate groups tend to remain in contact with the surrounding water molecules driven by these two forces, soap molecules spontaneously cluster into micelles
17 Soaps and Detergents
17-13
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
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 fat stains, the nonpolar parts of the soap micelles dissolve nonpolar dirt molecules and they are carried away in the polar wash water
17 Soaps and Detergents
17-14
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Soaps form water-insoluble salts when used in water containing Ca(II), Mg(II), and Fe(III) ions (hard water)
+ 2+ 2 CH3 ( CH2 ) 1 4 CO2 Na + Ca A sodium soap (soluble in water as micelles)
17 Soaps and Detergents
[ CH3 ( CH2 ) 1 4 CO2 ] 2 Ca Calcium salt of a fatty acid (insoluble in water)
2+
2 Na
17-15
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
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
17 Synthetic Detergents
The most widely used synthetic detergents are the linear alkylbenzene sulfonates (LAS)
17-16
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Soaps and Detergents
CH3 ( CH2 ) 1 0 CH2 Dodecylbenzene CH3 ( CH2 ) 1 0 CH2 SO3
-
1 . H2 SO4 2 . Na OH
Na
Sodium 4-dodecylbenzenesulfonate (an anionic detergent)
Also added to detergent preparations are
foam stabilizers bleaches optical brighteners
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17-17
Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid
9 10 11 12 13 14 15 16 17 18 19 20 7 8 6 5 4 3 2 1
17 Prostaglandins
CO2 H
Prostanoic acid
17-18
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
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 9 8 6 5 arachidonic acid CO2 H
11 12 14
17 Prostaglandins
15
Arachidonic acid
17-19
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Prostaglandins
9
among the prostaglandins synthesized from arachidonic acid are O
CO2 H
11
15
HO HO H
PGE2
HO
9
CO2 H HO
11
15
HO H
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
PGF2
17-20
Research on the involvement of PGs in reproductive physiology has produced several clinically useful derivatives
15-Methyl-PGF2 is used as a therapeutic abortifacient
HO
9
17 Prostaglandins
extra methyl group at carbon-15 CO2 H
HO
11
15
HO CH 3 15-Methyl-PGF
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17-21
17 Prostaglandins
the PGE1 analog, misoprostol, is used for prevention of ulceration associated with the use of aspirin-like NSAIDs O CO2 H PGE1
15 16
HO O
HO H HO CO2 CH3 CH3
16
HO
15
Misoprostol
17-22
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Steroids: a group of plant and animal lipids that have this tetracyclic ring structure
17 Steroids
C A B
17-23
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Common Features
CH 3 H H CH 3 H H
the fusion of rings is trans and each atom or group of atoms at a ring junction is axial the pattern of atoms or groups of atoms along the ring junctions is nearly always trans-anti-trans-anti-trans the steroid system is nearly flat and quite rigid many have axial methyl groups at C-10 and C-13
17-24
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Cholesterol
H3 C H3 C H HO H H
17-25
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Androgens - male sex hormones
synthesized in the testes responsible for the development of male secondary sex characteristics
H3 C H3 C H O Testosterone H H HO Androsterone
17-26
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Androgens
OH H H3 C H
H3 C H H
Among the synthetic anabolic steroids are
H3 C H3 C
2 1
17 Anabolic Steroids
OH CH 3
17
H H H
H3 C H3 C N N H A H H H
OH CH3
O Methandrostenolone
H Stanozolol
17-27
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Estrogens - female sex hormones
synthesized in the ovaries responsible for the development of female secondary sex characteristics and control of the menstrual cycle CH 3
17 Estrogens
H 3 C C=O H H3 C H O Progesterone
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
H3 C H
H H HO H
Estrone
17-28
Progesterone-like analogs are used in oral HO C CH contraceptives H C
"Nor" refers to the absence of a methyl group here. It is present in ethindrone O
3
17 Synthetic Estrogens
H H H
H Norethindrone
17-29
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Glucorticoid Hormones
synthesized in the adrenal cortex regulate metabolism of carbohydrates decrease inflammation involved in the reaction to stress
CH2 OH O H3 C H O Cortisone
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
CH2 OH HO H3 C C=O H3 C OH H H H
17-30
H3 C H H
C=O OH
O Cortisol
17 Mineralocorticoid Horm.
OH O H3 C H O Aldosterone H H CH CH2 OH C= O
synthesized in the adrenal cortex regulates blood pressure and volume by stimulating the kidneys to absorb Na+ , Cl-, and HCO3-
17-31
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 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 H3 C
H3 C H H H CO2 H
HO
OH H Cholic acid
17-32
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Biosynthesis of Steroids
all carbon atoms of cholesterol are derived from the two carbon acetyl group of acetyl-CoA cholesterol is, in turn, the starting material for the synthesis of these classes of compounds
bile acids (e.g., cholic acid) Cholesterol sex hormones (e.g., testosterone and estrone) mineralocorticoid homones (e.g., aldosterone) glucocorticoid hormones (e.g., cortisone)
17-33
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
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)
17-34
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Phospholipids
A phosphatidic acid
stearic acid
17 Phospholipids
O CH 2 -O- P- O O OO CH O CH 2 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
17-35
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Phospholipids
Name and Formula ethanolamine HOCH 2 CH 2 NH 2 choline + HOCH 2 CH 2 N( CH 3 ) 3 serine HOCH 2 CH CO 2 NH 3 inositol HO HO
+
Name of Phospholipid phosphatidylethanolamine (cephalin) phosphatidylcholine (lecithin) phosphatidylserine OH
HO
OH
OH phosphatidylinositol
17-36
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
A lecithin
17 Phospholipids
O stearic acid O
2
choline
+
O P OCH 2 CH 2 N( CH 3 ) 3 O CH O CH O CH 2 glycerol
palmitic acid
in aqueous solution, phospholipids spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers
17-37
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 A Lecithin
17-38
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
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 floatin 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
17 Biological Membranes
17-39
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
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
17 Fat-Soluble Vitamins
The fat-soluble vitamins include A, D, E, and K
17-40
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Vitamin A, or retinol, occurs only in the animal world
CH 3 CH 3 CH 3 Retinol (Vitamin A) CH 3 CH 3 CH 2 OH
17 Vitamin A
Vitamin A is found in the plant world in the form of a provitamin in a group of pigments called carotenes (tetraterpenes)
enzyme-catalyzed cleavage of b-carotene followed by reduction gives two molecules of vitamin A
17-41
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Vitamin A
CH 3 CH 3 CH 3 b- Carotene CH 3 CH 3
site of cleavage
H3 C H3 C
CH 3
CH 3
CH 3
enzyme-catalyzed cleavage and reduction in the liver CH 3 CH 3 CH 3 Retinol (Vitamin A)
17-42
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
CH 3
CH 3 CH 2 OH
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
17 Vitamin A
17-43
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Vitamin A
CH3 CH3 CH3 H3C CH3
11
11-12 cis configuration
12
CH=N-opsin light
CH3 CH3 CH3
CH3
11 12
CH3 CH=N-opsin
17-44
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
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
17 Vitamin D
HO Vitamin D 3
17-45
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
Vitamin E: a group of compounds of similar structure
the most active is -tocopherol
OH H3 C H3 C O H3 C CH3 Four isoprene units, joined head-to-tail, beginning here and ending at the aromatic ring CH3 CH3 CH3 CH3 Vitamin E ( -Tocopherol)
17-46
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17 Vitamin E
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
17 Vitamin E
17-47
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
The name of this vitamin comes from the German word Koagulation, signifying its important role in the blood-clotting process
O CH3 3 isoprene units
17 Vitamin K
O Vitamin K1
O CH3 3
Menadione O (a synthetic vitamin K analog)
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
17-48
17
Lipids
End Chapter 17
17-49
Copyright 2000 by John Wiley & Sons, Inc. All rights reserved.
