Introduction to Pharmaceutical Chemistry PF1009 Lecture Notes PDF

Introduction to Pharmaceutical Chemistry PF1009 Dr Tim O’Sullivan Office 2.05 - Cavanagh Building [email protected]  Topic s Nomenclatu Carbonyls re...

Introduction to Pharmaceutical Chemistry PF1009 Dr Tim O’Sullivan Office 2.05 - Cavanagh Building [email protected]  Topic s Nomenclatu Carbonyls re Carboxylic acids Alkanes Esters Alkenes Acid chlorides/ Alkynes anhydrides Alkyl halides Amides Alcohols Aromatics Epoxides Amines P1 Lectures Wednesday 3-4pm LG52  Text s Organic Chemistry – J. McMurry Beginning Organic Chemistry : Workbook 2 – G. L. Patrick (An Introduction to Medicinal Chemistry – G.L. Patrick ) Partial notes are available on Canvas – print out and bring to lectures  Treatment of Disease Two main approaches: –Surgical Labour intensive Time demanding Limited number of individuals Rich nations –Medical Based on drug molecules Large number of people Shorter time frame Developed and developing countries  Impact of Therapeutic Drugs Second only to public health measures Penicillin reduced bacterial meningitis to treatable disease. 100 g of salbutamol sulfate relieves asthma attack Intravenous 2 mg of lorazepam stops life- threatening seizures (status epilepticus) Myocardial infarction treated with 8-10 mg of morphine.  What is a ‘drug molecule’? 1 or more functional groups Arranged in a defined 3D space on structural framework Enables molecule to bind specifically to a receptor Promotes a beneficial biological response Precludes binding to untargetted receptors minimizes toxicity. Rigid framework which reduces flexibility & prevents binding to secondary targets Withstand journey from point of administration to interaction with receptor  Aspirin (acetylsalicyclic acid)  Organic chemistry Definition - A branch of chemistry dedicated to the study of the structures, synthesis, and reactions of carbon-containing compounds “The chemistry of life” Focus on elements C, H, N, O, P, S, X (Halides)  Understanding Organic Structures Palytoxin – deadliest, naturally occuring compound 10.5 μg to kill 70 Kg person (1 grain sand = 2mg) C128H221N3O54 Molecular, Structural & Empirical Formulae C6H14O2 C3H7O  Isomer s Structural Isomers are compounds with the same molecular formula but different structural formula. Structural Isomers C2H include ethanol and of ether 6O dimethyl H H H ethanol H H C C H H H OH C O C H dimethyl ether H H Other types of isomers : regioisomers, stereoisomers etc…  Hydrocarbon Framework H H H H Chains H C C C C H H H H H H H H H H C C C C H Branched H C H Chains H H H H H H H C H C C H H Ring H C C H s C H H H H Combinations of the above  Functional “Part of a molecule with theGroups potential to take part in a chemical reaction of interaction. FGs determine the way a molecule behaves both chemically and biologically. morphine alcohol HO ether O N HO alkene a m i n e H Drawing molecules H H H O H C H C C C C C OH H H H H trans-2-Hexenoic acid IUPAC name CH3CH2CH2CH=CHCO2H Condensed structural formula Line-segment formula  Guidelines for Drawing Molecules 1. Draw chains as zigzag line 2. In general, omit on Hs attached to carbon along with other C-H bondsatoms, 3. In general, miss out capital Cs representing carbon atoms in skeletal formulas 4. May insert Cs and Hs when part of a functional group  Example s H H H H C H C C H H C C H C H H H H H H HH H C C H HC C C H HH H H  Odd One Out? O NH2 OH OH N O H H Leucine NH2 HO2C NH2 HOOC  Representing 3D Information wedg – coming out from plane of es paper dashes – going behind plane of paper  Names of Carbon Chains Number of Name of group Formula Abbreviation Name of alkane carbon atoms (chain+H) in chain 1 Me. Methyl -CH3 Methane Et. 2 Ethyl -CH2CH3 Ethane Pr 3 Propyl -CH2CH2CH3 Propane Bu 4 Butyl -(CH2)3CH3 Butane 5 Pentyl -(CH2)4CH3 - Pentane 6 Hexyl -(CH2)5CH3 - Hexane 7 Heptyl -(CH2)6CH3 - Heptane 8 Octyl -(CH2)7CH3 - Octane 9 Nonyl -(CH2)8CH3 - Nonane 10 Decyl -(CH2)9CH3 - Decane  Usage of Abbreviations Can only be used forterminal chains of atoms O O O OBu Corre ct NH2 H2N OH Bu O Incorrec t  Branched Chains n- n-BuOH OH (normal) n-Butanol iso- / i- i-BuOH (isomer) OH i-Butanol sec- sec-BuOH (secondary) OH sec-Butanol tert- / t- t-BuOH (tertiary) OH t-Butanol Note: n- (=normal)  N- (=nitrogen) (attached to Nitrogen)  Carbon Rings Rings of carbon atoms have prefix ‘cyclo’ Non-planar structure e.g. cyclohexane has chair or boat shape Structure Name Cyclopropane Cyclobutan e cyclohexa ne Cyclopenta ne  Common Functional Groups I Alkanes – contain no functional groups -ane Alkenes – contain C=C double bonds (olefins) -ene Alkynes – contain CC triple bonds -yne Alcohols – R-OH : contain a hydroxyl (OH) -ol Ethers – R1-O-R2 : contain an alkoxy group (- OR) X Y ether Amines – R-NH2 : contain an amino (NH2) group -amine or amino-  Common Functional Groups Alkyl halides II – R-X : contain a halide (-F, -Cl, -Br, -I) group Halo- or -halide Aldehydes (R-CHO) : contain a carbonyl group (C=O) -al Ketones (R1-CO-R2) : contain a carbonyl group (C=O) -one Carboxylic acids – R-CO2H : contain a carboxyl (-CO2H) group -oic acid Esters – R1-CO2R2 : contain a carboxyl group with an extra alkyl (CO2R) -ate Nitriles or Cyanides – R-CN : contain a cyano (nitrile) group cyano- or -nitrile  Systematic Nomenclature I Series of rules drawn up by IUPAC Suffix corresponds to FG e.g. –ane for alkane, -ol for alcohol Prefix indicates number of C atoms e.g. meth- (1), eth- (2) etc. ethanol butyn e  Systematic Nomenclature II Branched compounds are named as alkyl derivatives of the _longest_ straight chain in the molecule The length of the longest chain provides the parent name The straight chain is numbered from the end which produces the smaller numbers for the carbon atoms which occur at the branches A hyphen must separate numbers from names and prefixes Numbers may also be used for FGs which are not at a terminal carbon i.e. substituents on the chain The straight chain is numbered from the end which produces the smaller numbers for the carbon atoms which occur at the FG butan 1- e propanol  Systematic Nomenclature III (Alkanes) Multiple substituents are shown by di, tri, tetra (not tert!), penta Number the C-atoms from the end of the chain that will give the lowest set of numbers If two possible sets are equal, choose the numbering that give the lowest number to the substituent that comes first alphabetically. Substituents should be listed in alphabetical order Ignore multiplying prefixes when alphabetizing e.g. treat dimethyl as 'm' not 'd 2,2-dimethylbutane 2,4-dimethylpentane 2,3-dimethylpentane 3-ethyl-2-methylpentane ( not 3,4- ( not 3-ethyl-4- dimethylpentane) methylpentane)  Systematic Nomenclature IV When a FG is present, number chain such that FG gets lowest number Characteristic groups cited only as prefixes in substitutive nomenclature e.g. halogens Terminal functional groups are assumed to Carbon e.g be on car aldehydes, carboxylic acids etc. 1. OH O 4-methyl-2- 4-methyl-2-pentanone 2,4-dimethyl-1-pentene pentanol  Nomenclature MCQ I 1. What is the IUPAC name 2. The correct IUPAC name for for: the following compound is: a. 2,3,4,5,6,7,8-heptamethylnonane a. Dimethylpentene b. 1,2,3,4,5-pentamethyl-2,5- b. 4,4-Dimethyl-1- isopropylpentane pentene c. 1,1',2,3,5,6,7,7'-nonamethylheptane c. 2,2-Dimethyl-4- d. di-(1,2,3-trimethylbutyl)ethane pentene e. None of the above d. 4,4,4-Trimethyl-1- butene e. 1,1,1-Trimethyl-3- butene  Trivial Names Some compounds are better known by their trivial names acetone Acetic acid ethan Methanoic (ethanoic Ethyl al acid acid) ethanoate OH N Toluene Pyridine Benzene pheno l  Important Molecular Fragments Some molecular fragments have important mechanistic & stuctural significance Phenyl Benzyl (Ph) (Bn) PhOMe BnBr O O PF1009 Introduction to Pharmaceutical Chemistry Introductory Pharmaceutical Organic Chemistry Tutorial 1. 1. Provide systematic names for the following molecules. In addition, provide the molecular formula for each compound. I i. ii. OH Br iii. iv. Br v. vi. OH 2.Provide line-segment diagrams (as per Question 1) for each of the following compounds. i. EtBr ii. BuOH iii. EtOAc iv. tert-BuNH2 v. BnCN vi. PhCl