ORGANIC AND BIOORGANIC CHEMISTRY

Transcription

1 P. GERGELY Department os Medical Chemistry Medical and Health Science Center University of Debrecen ORGANIC AND BIOORGANIC CHEMISTRY FÓR MEDICAL STUDENTS THIRD EDITION University of Debrecen Medical and Health Science Center 2004

2 CONTENTS IN BRIEF 1 INTRODUCTION 1 2 STEREOCHEMISTRY 13 3 HYDROCARBONS 33 4 AROMATIC COMPOUNDS 81 J ORGANIC HALOGÉN COMPOUNDS ALCOHOLS AND PHENOLS ETHERS SULFUR CONTAINING ORGANIC COMPOUNDS ALDEHYDES AND KETONES NITROGEN-CONTAIN1NG ORGANIC COMPOUNDS CARBOXYUC ACIDS CARBOXYUC ACID DERIVATIVES AMINO ACIDS PEPTIDES AND PROTEINS CARBOHYDRATES LIPIDS NUCLEOTIDES AND NUCLEIC ACIDS 361 INDEX 389

3 CONTENTS iii CONTENTS CHAPTER 1 INTRODUCTION Organic chemistry. The study of carbon compounds Carbon-carbon bonds Allotropie forms of carbon Carbon-heteroatom bonds Classification of organic compounds Electron distributions in organic compounds Chemical reactions in organic chemistry CHAPTER 2 STEREOCHEM ISTRY Chiral molecules Three-dimensional structures of enantiomers Properties of enantiomers Optical activity Relative and absolute configurations The D and L system: relative configuration The R-S system of absolute configuration Molecules with more than one stereocenters Chiral molecules without asymmetric atoms Stereochemistry öf Chemical reactions that produce chiral centers The origin of asymmetric biomolecules Separation of enantiomers: resolution CHAPTER 3 HYDROCARBONS Saturated hydrocarbons: alkanes (paraffms) Conformations of alkanes Constitutional (structural) isomerism of alkanes IUPAC nomenclature of alkanes Nomenclature of alkyl groups Physical properties of alkanes Petroleum and petróleum refining Cycloalkanes Conformations of cyclohexane Substituted cyclohexanes: axial and equatorial hydrogen atoms Distributed cyclohexanes: cis-trans isomerism Bicyclic alkanes

4 ÍV CONTENTS Chemical reactions of saturated hydrocarbons Combustion of alkanes Halogenation of alkanes Chlorination of methane Unsaturated hydrocarbons: alkenes and alkynes Nomenclature and structure of alkenes Cis-trans isomerism of alkenes 1,3-butadiene: electron delocalization The stability and light absorption of conjugated polyenes Addition reactions of alkenes Activation of the w bond Addition of hydrogén halides to alkenes Acid-catalyzed hydration of alkenes Addition of halogens to alkenes Catalytic hydrogenation of alkenes Polymerization of alkenes Isoprenes: natural compounds with isoprene units Terpenes Somé important terpenes Carotenes Vitamin A and the photochemistry of vision Alkynes Structure and bonding in acetylene Addition reactions of alkynes CHAPTER 4 AROMATIC COMPOUNDS Structure and bonding of benzene The Kekulé structure fór benzene Structure of benzene Resonance theory fór the stability of benzene Aromaticity and Hückel s rule Nomenclature of aromatic compounds Properties of aromatic hydrocarbons Benzene and its derivatives Polycyclic aromatic hydrocarbons Heterocyclic aromatic compounds Aromaticity of five-membered heterocycles Aromaticity of six-membered heterocycles Chemical reactions of aromatic compounds Mechanism of electrophilic aromatic substitution Electrophilic substitution reaction of benzene with bromine Effect of substituents: reactivity and orientation Reactivity of polycyclic and heterocyclic aromatic compounds Oxidation

5 CONTENTS V CHAPTER 5 ORGANIC HALOGÉN COMPOUNDS 107 Chemical reactions of halogén compounds 107 Nucleophilic substitution 108 Elimination reactions 110 Important halogenated compounds 110 CHAPTER 6 ALCOHOLS AND PHENOLS 115 Classification of alcohols and phenols 115 Physical properties of alcohols and phenols 118 Synthesis of alcohols and phenols 120 Chemical properties of alcohols and phenols 122 The acidity of alcohols and phenols 122 Preparation of ethers 124 Dehydration of alcohols 124 Formation of esters 125 Oxidation of alcohols and phenols 125 Biological oxidation of alcohols 126 Oxidation of phenols 126 Important alcohols and phenols 127 Derivatives of alcohols and phenols 130 CHAPTER 7 ETHERS 133 Preparation of ethers 134 Properties of ethers 135 Important ethers 135 CHAPTER 8 SULFUR CONTAINING ORGANIC COMPOUNDS 139 Thiols (mercaptans) 140 Thioethers 141 CHAPTER 9 ALDEHYDES AND KETONES 143 Nomenclature of aldehydes and ketones 143 Structure and bonding of the carbonyl group 144 Physical properties of aldehydes and ketones 145 Synthesis of aldehydes and ketones 146 Reactions of aldehydes and ketones 147 Nucleophilic addition reactions 147 Hydrates 147 Hemiacetals and hemiketals 148 Acetals 148 Addition of hydrogen cyanide 149 Addition of ammónia 149

6 vi CONTENTS Condensation reactions 149 Oxidation and reduction reactions 150 Keto and enol tautomers 151 Enol compounds in cellular processes 153 Aldol addition and aldol condensation 154 Aldol condensations in the biological processes 155 Important aldehydes and ketones 156 Quinones 159 Natural quinones as reversible oxidizing agents 160 CHAPTER 10 NITROGEN-CONTAINING ORGANIC COMPOUNDS 163 Amines 163 Physical properties of amines 165 Preparation of amines 166 Chemical properties of amines 167 Amines as bases 168 Ammonium salts 170 Quaternary ammonium salts 170 Reactions of amines 171 Schiff s base formation 171 Acylation reaction 171 Reactions of amines with nitrous acid 171 Biologically important amines 173 Amines as neurotransmitters 175 Pyrimidine and purine bases 177 Biologically important derivatives of heterocyclic compounds containing nitrogén atom 178 Five-membered heterocycles 179 Six-membered heterocycles 181 Polycyclic compounds containing nitrogén heteroatom 184 Colored compounds and dyes 186 The sulfa drugs 189 Alkaloids 191 CHAPTER 11 CARBOXYLIC ACIDS 195 Nomenclature of carboxylic acids 195 Physical properties of carboxylic acid 198 Preparation of carboxylic acids 200 Chemical properties of carboxylic acids 201 Acidity of carboxylic acids 201 Salts of carboxylic acids 203 Decarboxylation reactions 204 Oxidation in biological systems 204 Important carboxylic acids 206 Fatty acids 210 Detergents 212 Prostaglandins 215

7 CONTENTS vii Hydroxy acids 217 Important hydroxy acids 218 Keto acids 220 Ketone bodies 222 The tricarboxylic acid cycle 225 Reactions of the tricarboxylic acid cycle 226 CHAPTER 12 CARBOXYLIC ACID DERIVATIVES 229 Esters of carboxylic acids 229 Preparation of esters 230 The mechanism of acid-catalyzed esterification 230 Saponification of esters 231 Importáru esters 232 Thioesters 234 Carboxylic acid anhydrides 235 Acyl halides 236 Amides 237 Dérivativés of carbonic acid 238 CHAPTER 13 AMINO ACIDS 243 Structure of amino acids 243 Classification of amino acids found in proteins 244 Nonpolar (hydrophobic) side chains 244 Polar (uncharged) side chains 245 Negatively charged (acidic) side chains 245 Positively charged (basic) side chains 246 Nonstandard amino acids 246 Stereochemistry of amino acids 248 Absorption of light by amino acids 249 Acid-base behavior of amino acids 250 Reactions of amino acids 254 Specific reactions of the amino group 254 Specific reactions of the carboxyl group 258 Separation of amino acids 259 Electrophoresis of amino acid mixtures 260 Ion-exchange chromatography 260 High-performance liquid chromatography 261 CHAPTER 14 PEPTIDES AND PROTEINS 263 Stereochemistry of the peptide bond 264 The amino acid sequence of polypeptide chains: Principle of sequence analysis 266 Identification of amino- and carboxyl-terminál residues 266 Cleaving the polypeptide chain 267 The Edman degradation 267

8 viii CONTENTS Ordering peptide fragments Chemical synthesis of peptides Naturally occurring peptides Structure and function of proteins Functional roles of proteins Physical and Chemical properties of proteins Purification of proteins The three-dimensional structure of proteins The secondary structure of proteins Tertiary structure: the conformation of globular proteins Tertiary structure is determined by amino acid sequence Common structural pattems in the conformation of proteins Protein quatemary structure CHAPTER 15 C ARB OHYDR ATES Monosaccharides Configurations of monosaccharides: D and L designations Determination of the configurations of monosaccharides The cyclic structures of monosaccharides Furanose structures Pyranose structures Mutarotation Chemical reactions of monosaccharides Reduction of monosaccharides Oxidation of monosaccharides Identification of aldoses and ketoses by oxidizing agents Reactions at the hydroxyl groups Common monosaccharides Derivatives of monosaccharides Glycosides Deoxy and amino sugars Glycolysis: importance of phosphorylated intermediates Disaccharides Nonreducing disaccharides Sucrose Sweeteners in food Reducing disaccharides Oligosaccharides of glycoproteins Polysaccharides Energy-storing homopolysaccharides Starch Glycogen Structural homopolysaccharides Heteropolysaccharides: glycosaminoglycans, and their complexes: proteoglycans The structure of bacterial cell wall

9 CONTENTS ix CHAPTER 16 LIPIDS 335 Glycerophospholipids 337 Sphingolipids 342 Steroids 344 Cholesterol 345 The structure of biological membranes 348 The lipid bilayer 348 The fluid raosaic model fór membráné structure 351 Steroids with specific biological fimctions 353 Vitamin D 354 Bile acids 355 Steroid hormones 356 Corticosteroids 357 Sex hormones 358 Steroid glycosides 359 CHAPTER 17 NUCLEOTIDES AND NUCLEIC ACIDS 361 Nucleotides 361 Pyridine and purine bases 362 Nucleosides 363 Nucleotides 365 Nucleotide coenzymes 369 Polynucleotídes 371 Chemical structure of DNA 372 DNA double helix 375 Denaturation of double-stranded DNA 378 Principle ofhybridization 380 Types of DNA structure 380 Determination of DNA sequences 381 Chemical structure of RNA 385 Secondary and tertiary structures of RNA 385 Types of RNA 388 INDEX 389