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Lecture 2: Organic chemistry

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Organic chemistry:*

3CH-2CH-R "Paraffins": I.Alkanes

*lipid soluble (water insoluble) *stable

3.CH-CH (OH)-*side chain hydroxylation may occur: R

2CH=CH-R "Olefins": II.Alkenes

*lipid soluble (water insoluble), & also aqueous acid or base insoluble.

*Reactions:

: oxidation→ peroxides, halogenations.in vitro "on shelf"a.

: peroxidation, hydration & reduction.. in vivob

:Alcohols III.

O & aqueous solution & lipid.2*Soluble in H OH:2CH-alcohol: Rry 1

*Oxidized to aldehyde (CHO)→ Acid (COOH).

C=O–OH: *Oxidized to ketone -CH-R alcoholry 2

3CH

3 CH

OH: → No oxidation (no H atom).-C-: Ralcoholry 3

3CH

O solubility.2dipole bonds which is responsible for H -Dipole forms

:R-O-R Ethers IV.

O solubility & lipid soluble.2*Partial H

*Reactions: *in vitro→ peroxides.

*in vivo→ O-dealkylation.

:CHO-R Aldehydes V.

O Solubility).2*Lipid soluble (↓ M.wt→ ↑H

:* in vitro→ reduction, oxidation & polymerization.reaction*

*in vivo→ oxidation & aromatic hydroxylation

:Amines VI.

O sol.2Low M.wt → H 2 NH2CH-R ry1

NHR High M.wt → lipid sol. 2CH-R ry2

2 NR2CH-R ry3

→ the most basic3R+N2CH-R ry4

**Reaction:

oxidationIn vitro: →

dation, sulfation & methylation.In vivo: glucuroni

→ Oxidative deamination.ry1

dealkylation-→ N ry2

oxidation.-→ Nry3

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:COOH-R acid: Carboxylic VII.

O solubility, while, ↑M.wt→↑ lipid solubility.2↓ M.wt→↑H

*Reaction: salt formation, ester formation & decarboxylation.

*Stable on shelf.

*in vivo: *Conjugation with Glucuronic acid, Glycine & Glutamine.

* − oxidation.

:C=O2R Ketones VIII.

O solubility)2*Lipid soluble (↓ M.wt→↑H

*In vitro: very stable.

*In vivo: undergoes some oxidation or reduction reaction.

:Amides IX.

*lipid soluble.

*In vitro: very stable.

In vivo: enzymatic hydrolysis by amidase enzyme →ammonia + acid.

:O2RCOOR'+H OH→-R' + COOH-R :Esters X.

*Lipid soluble.

*In vitro: hydrolysis.

*In vivo: enzymatic hydrolysis by esterase.

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*Stereochemistry:

: compounds in which all atoms are bonded in the same way but Stereoisomers*

differ in their space orientation.

.and Conformational: Optical, Geometric, divided intoThey are -

compound has same molecular formula but differ in at A. Optical Isomers:

carbon atom (4sustituents). 1 asymmetric (chiral)least

nother (sameof one a mirror imagesoptical isomers that are : Enantiomers1.

physical & chemical properties) & rotation of plane polarized light is the same

but opposite in direction.

ion of plane of polarized light=clockwise rotatDextrorotatory+ *D

wise.Levorotatory= anticlock -*L

: equal amount of D & L & is optically inactive.mixture Racemic

**Enantiomers can have large differences in potency, biological activity,

metabolism because of a non complete interaction with the receptor.

are stereoisomers which are centers):2. Diastereomers (at least 2 chiral

neither Mirror images nor Superimosable.

(special Diastereomers) through epimerization, structurally identical 3. Epimers:

except in one chiral center.

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results of restricted rotation about double Isomers:B. Geometric

bond=rigid ring system.

E.g. Cis-trans isomers

C. Conformational Isomers (Rotamers, conformers) (Trans &

Gauche):

It is the non identical special arrangement of atom in a molecule, which results

bond.ingle rotation around one or more Sfrom

drugs containing different D. Bioisosters (Isosteric analogue):

groups but are spatially & Electronically equivalent & so can be

interchangeable (Isosteric replacement) without big differences in

physiochemical properties but with better potency, less SE, longer duration.

flurouracil.-5 ) uracil &: 1Examples

2) Procainamide & procaine:

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Extra notes:

nion resonance (basic in origin).: is a weak acid due to stable aPhenol*

Reaction of +Na OH is electrophilic substitution.

*perchloro acetic acid is stronger than acetic acid because it can protonate it.

CCl?3 )3CHCl, (CH2)3Cl, (CH2CH3CHCl, 3*Which is more reactive: CH

CCl → because R is electron donating3 )3(CH

*Fixed oil hydrolysis→ glycerol + free fatty acid.

*In assay of amphetamine in plasma, it is extracted with ether.

salts. can react with both acids & bases to formAmphoteric agents *

Eg.

we can obtain dicarbonyl compound by Claisen condensation:*

(ethyl aceto acetate).3 CH2COOCOCH5H2ethyl acetate) → C-COOH (25H22C

is R Mg X (not react with cyclohexane BUT can react with Grignard reagents*

cyclohexene).

Should react with c=c:

c=c + R Mg X→R-C-C-MgX

*Nucleophilic substitution:

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Chemical structures:

Imidazole* Pyrazole* Pyrrole* Thiophen* Furan*

Triazole* Thiazole* Oxazole* Isoxazole *

Piperazine* Pyrimidine* Pyrazine* Pyridazine*

Quinolone* Pyrrolidine* Piperidine* Pyridine*

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Heroin=diacetyl morphine* Codeine* Morphine*

*Naloxone Oxycodone* Hydromorphone*

Diphenoxylate* Mepridine=Pethidine *

Propoxyphene* Methadone*

*Mefenamic acid

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*Phenylbutazone *Diflunisal

Ibuprofen* Indomethacin* Naproxen*

*Piroxicam.

derivative. acid :acetic Indomethacin while derivative acid propionic :Ibuprofen :N.B

*Warfarin *Dicumarol *Ticlopidine

*Methacholine

*Carbachol *Bethanechol

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*Suxamethonium *Decamethonium

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*Penicillins side chains:

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