Organic Chemistry

Organic Chemistry William H. Brown & Christopher S. Foote

Lipids Chapter 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

Triglycerides • Triglyceride:an ester of glycerol with three fatty acids

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

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

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

Soaps and Detergents • Natural soaps are prepared by boiling lard or other animal fat with NaOH, in a reaction called saponification (Latin, sapo, soap)

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

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

Soaps and Detergents • Soaps form water-insoluble salts when used in water containing Ca(II), Mg(II), and Fe(III) ions (hard water)

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)

Soaps and Detergents • Also added to detergent preparations are • foam stabilizers • bleaches • optical brighteners

Prostaglandins • Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid

Prostaglandins • Prostaglandins are not stored in tissues as such, but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific physiological triggers • one such polyunsaturated fatty acid is arachidonic acid

Prostaglandins • among the prostaglandins synthesized biochemically from arachidonic acid are

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

Prostaglandins • the PGE1 analog, misoprostol, is used to prevent the ulceration associated with the use of aspirin-like NSAIDs

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

Eicosanoids • Leukotrienes are found primarily in white blood cells. One function is constriction of smooth muscles, especially those of the lungs

Steroids • Steroids: a group of plant and animal lipids that have this tetracyclic ring structure • The features common to the ring system of most naturally occurring steroids are illustrated on the next screen

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

Cholesterol

Androgens • Androgens - male sex hormones • synthesized in the testes • responsible for the development of male secondary sex characteristics

Anabolic Steroids • Among the synthetic anabolic steroids are

Estrogens • Estrogens - female sex hormones • synthesized in the ovaries • responsible for the development of female secondary sex characteristics and control of the menstrual cycle

Synthetic Estrogens • Progesterone-like analogs are used in oral contraceptives

Glucorticoid Hormones • synthesized in the adrenal cortex • regulate metabolism of carbohydrates • decrease inflammation • involved in the reaction to stress

Mineralocorticoid Horm. • synthesized in the adrenal cortex • regulate blood pressure and volume by stimulating the kidneys to absorb Na+, Cl-, and HCO3-

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

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

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)

Phospholipids • A phosphatidic acid • further esterification with a low-molecular weight alcohol gives a phospholipid • among the most common of these low-molecular-weight alcohols are

Phospholipids • among the most common of these low-molecular-weight alcohols are

Phospholipids • A lecithin in aqueous solution, phospholipids spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers

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

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

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

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

Vitamin A

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

Vitamin E • Vitamin E is a group of compounds of similar structure, the most active of which is -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

Vitamin K • The name of this vitamin comes from the German word Koagulation, signifying its important role in the blood-clotting process

Prob 26.12 Account for the detergent properties of each compound.

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 1-chlorohexadecane (cetyl chloride), and to N,N-dimethylhexadecanamine.

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.

Prob 26.18 Compare the structural formulas of unoprostone and PGF2a.

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.

Organic Chemistry