Heterofunctional Compounds (Lecture) PDF

HETEROFUNCTIONAL COMPOUNDS Heterofunctional compounds contain several different functional groups in structure: -OH ( hydroxyl- group), -NH2 ( amino - group), -COOH ( carboxyl - group ), -C=O (carbonyl - group) and others. The majority of organic compounds in the body are heterofunctiona...

HETEROFUNCTIONAL COMPOUNDS Heterofunctional compounds contain several different functional groups in structure: -OH ( hydroxyl- group), -NH2 ( amino - group), -COOH ( carboxyl - group ), -C=O (carbonyl - group) and others. The majority of organic compounds in the body are heterofunctional. A great deal of them is presented as the following:  amino alcohols  hydroxyacids  ketoacids  amino acids Amino alcohols Amino alcohols contain amino- and hydroxyl- (alcohol) groups: therefore they have both alcohol and basic properties. Colamine. (2-aminoethan-1-ol), (ethanolamine). It’s formed by amino acid Serine decarboxylation in organism: H2C CH COOH - CO2 H2C CH2 OH NH2 OH NH2 Serine Ethanolamine Choline. CH2 CH2 N+ (CH3)3 OH- OH Choline It can be formed by ethanolamine methylation: CH3 CH2 CH2 + 3CH3-I CH2 CH2 N + CH3 OH- CH3 OH NH2 + NaOH OH Ethanolamine and choline are the structural components of phospholipids (kefaline and lecithine accordingly). Choline takes part in lipid turnover regulation and prevents liver lipid degeneration. Amino alcohols can form esters by hydroxyl-group with caborxylic acids. Acetylcholine is one of the most important in human body which serves as transmitter (mediator) in nerves system: Cl OH- - OH CH2 CH2 N+ (CH3)3 CH2 CH2 N+ (CH3)3 CH3 C O O OH - HCl CO Choline CH3 Acetylcholine  Synthesis of acetylcholine occurs in the cytosol of nerve terminal, employing the enzyme choline acetyltransferase and stored in the synaptic vesicles: Acetyl-CoA + choline Acetylcholine + CoA Enzyme Acetylcholine is easily hydrolyzed to choline and acetic acid by enzyme acetylcholinesterase: OH- OH CH2 CH2 N + (CH3)3 - CH3 C OH- O CH2 CH2 N+ (CH3)3 +H2O O enzyme OH CO CH3 Acetylcholine Choline Aminophenols. OH OH OH CH2 CH2 NH2 CH CH2 NH CH CH2 NH2 OH OH DOPamine OH OH CH3 OH DOPAamine Norepinephrine (it is Ephinephrine ( it is (dophamine) formed by partial formed by methylation oxidation of dophamine of norepinephrine) Epinephrine and norepinephrine (adrenaline and noradrenaline or catecholamine) are hormones of adrenal medulla and neurotransmitters (neuromediators) formed from tyrosine in the human body. Hydroxyacids. Hydroxyacids are carboxylic acid derivatives, in which one or several hydrogen atoms in hydrocarbon radical are replaced for hydroxyl group (-OH). Hydroxyacid Isomerism. Hydroxyacids are characterized by two types of isomerism: 1.Structural isomerism. Structural isomerism is defined as isomerism of hydrocarbon chain structure and alcohol group location. It may be unbranched and branched chain structures and -, -, - dispositions of hydroxyl groups. 2.Stereoisomerism. Compounds that have the same molecular and structural formulae but differ in the three-dimensional arrangement of the atoms in space (spatial configuration) are termed as stereoisomers. They can be divided into two types:  1. Enantiomers 2. Diastereomers 1.Enantiomers (optical isomers). Enantiomers have the similar or identical chemical properties but differ in a characteristic physical property, their interaction with plane-polarized light: they rotate the plane of plane-polarized light in opposite directions. The ability of compound to rotate the plane-polarized light is named optical activity. When formula beam of plane-polarized light passes through a solution of an optical isomer, it will be rotated either to the right (dextrorotary «+»), or to the left (levorotary «-»). Rotation sign is defined experimentally by polarimeter. The asymmetric atom presence in molecule is the cause of optical activity. A carbon atom with four different substituents as said to be asymmetric (a chiral center) marked with an asterisk (). The presence of asymmetric atom in molecule results in the absence of symmetry elements: an axis of symmetry, a plane of symmetry etc. Molecules containing asymmetric atoms are named «chiralic» (from Greek word chiros, “hand”). Such molecules are nonsuperimposible mirror image of each other. A molecule with only one chiral carbon can have two stereoisomers; when two or more (n) chiral carbons are present, there can be 2n stereoisomers. The designation of a isomer as the D-form or its mirror image L-form is determined by its spatial relationships to parent compound of the carbohydrate family, the three-carbon sugar glyceraldehyde: Configuration of the nearest group to the asymmetric carbon atom (carboxyl or carbonyl) is named the « oxyacidic key»: H O C * CH OH CH2 OH Enantiomers are represented by Fisher-formulae, where the asymmetric carbon atom is not marked:  H O H O C C H OH HO H CH2 OH CH2 OH D(+) L(-) Different enantiomers possess different biological activity. 2.Diastereomers. Diastereomers are the stereoisomers that are not mirror image of each other and they are physically and chemically different compounds. For example: wine and mezo-wine acids (tartaric acids): COOH COOH H C OH H C OH HO C H H C OH COOH COOH D-wine Mezo-wine acid The main representatives of hydroxyacids: 1. Lactic acid , salt - lactate: COOH COOH H C OH HO C H CH3 CH3 D(-) Lactic acid L(+) Lactic acid L(+) lactic acid is naturally formed by glucose oxidation in anaerobic conditions. 2. Wine acid ( tartaric acid), salt - tartar. It has two asymmetric carbons:  COOH COOH H C OH HO C H HO C H H C OH COOH COOH D(+) Wine acid L(-) Wine acid A mixture of equal quantities of D- and L- wine acids is known as a grape acid. An equimolar solution of D- and L-enantiomers is referred to as racemic mixture and shows no optical rotation (because levorotary compensate dextrorotary). Grape acid is a racemate of wine acid. 3. Citric acid , salt - citrate: COOH CH2 It does not contain an asymmetric carbon (chiral center) and not rotate HO C COOH the plane of plane-polarized light. Citric acid is the metabolite of citric CH2 acid cycle. COOH 4. Malic acid, salt - malate: COOH H C OH CH2 Malic acid is a metabolite of citric acid cycle. COOH 5. β–hydroxybutiric acid, salts – hydroxybutirates CH3 H C OH CH2 COOH β-hydroxybutiric acid is formed in lipid catabolism, ketone body Hydroxyacids chemical properties.  As hydroxyacids are the heterofunctional compounds possessing both acid and alcohol properties. As acids they can form salts, esters, amides, halogen anhydrides. As alcohols they can be oxidized into ketoacids, can form ethers and esters. 1. Salts formation: CH3 CH COOH + NaOH CH3 CH COONa + H2O OH OH Lactic acid Sodium lactate 2. Esters formation with -COOH group: O CH3 CH COOH + HO-C2H5 CH3 CH C O C2H5 OH - H2O OH Lactic acid Ethyl ester of lactic acid 3. Esters formation with -OH group: O CH2 CH2 CH2 COOH + CH3-C CH2 CH2 CH2 COOH Cl - HCl O OH C O Acetylbutirate -hydroxybutiric acid CH3 4. Oxidation reaction: CH3 CH3 O CH OH C O -H2O COOH COOH Lactic acid Pyruvic acid Hydroxyacids specific reactions. 1. Specific reactions for  -hydroxy acids. a/ Cyclic anhydrides formation (lactides). It occurs by heating without mineral acids presence: O C OH OH O - 2 H2 O O C CH CH3 CH3 CH + CH CH3 O t CH3 CH C O OH OH C O Lactic acid b/ Splitting results in formic acid and aldehyde formation. It occurs by heating with mineral acids presence: OH H CH3 CH COOH HCOOH + CH3 C H2SO4 O t  Similar reaction can occur with citric acid: COOH COOH CH2 CH2 HCOOH + 2CO2 + H3C C CH3 HOOC C OH H2SO4 C O t O CH2 CH2 COOH COOH CO + H2O Therefore: Citric acid acetone + 2CO2 + CO + H2O t°  -Hydroxy acids specific reactions: Hydroxy acids form unsaturated acids by heating (elimination reaction): H3C CH CH2 COOH H2O + H3C CH CH COOH t OH Elimination can be possible due to CH-acid center formation by carbon atom: H H3C CH C COOH OH H ,, - Hydroxy acids specific reactions: Internal cyclic esters (lactones) formation is typical for these acids. Chiral conformation promotes the proceeding of the reaction thanks to the hydroxyl and carboxyl groups close position: O O C C CH2 OH CH2 H3C CH CH2 CH2 COOH O +H2O OH OH CH2 CH2 CH CH CH3 CH3 Lactones are unstable and easily hydrolyzed to the initial substrates in acid solutions:  O C CH2 + H2O O H3C CH CH2 CH2 COOH H+ CH2 OH CH CH3 Ketoacids (oxoacids). Ketoacids contain a carbonyl group in a radical: C = O They are subdivided into aldehydo- and keto-acids. Representatives. 1. Glyoxylic ( glyoxalic) acid , salts - glyoxylate: It’s found in immature fruits. O OH C C H O 2. Pyruvic acid, salts - pyruvate: CH3 C COOH O It’s formed as an intermediate metabolite in carbohydrate and amino acid pathways. 3. Acetoacetic acid,salts - acetoacetate (  -ketobutirate): CH3 C CH2 COOH O It’s formed in lipid metabolism (one of the ketone bodies). 4. Oxaloacetic ,salts - oxoloacetate (  - ketosuccinate): HOOC C CH2 COOH O It’s a metabolite of Citric Acid Cycle and also formed in amino acids metabolism. 5.  -ketoglutaric acid, salts α - ketoglutarate : HOOC C CH2 CH2 COOH O It’s a metabolite of Citric Acid Cycle, and formed in amino acid metabolism. Oxoacids are characterized by special dynamic isomerism - keto-enol tautomerism. Tautomerism is a coexistence of two isomers in solution in dynamic balance where they easily turned to each other. In case with oxoacids this passage is carried out between keto- and enol forms:  CH3 C COOH CH2 C COOH O OH keto-form enol-form Keto and enol forms can appear different properties. An enol -form can form esters using the -OH group. An ester of pyruvic enol -form and phosphoric acid has an important significance in organism: CH2 C COOH OPO3H2 Phosphoenolpyruvate. Keto-form can enter the reactions characterized for aldehydes and ketones. Chemical properties. 1. Decarboxilation of β-keto acids: CH3 CH3 C O C O CO2 + CH2 CH3 COOH aceton Besides that oxoacids possess all properties of carboxylic acids and oxocompounds. As carboxylic acids they form salts, esters, anhydrides etc. As oxocompounds they enter the oxidation, reduction, nucleophylic, substitution reactions etc.