Pharmaceutical Organic Chemistry - PowerPoint Presentation

Slide1

Pharmaceutical Organic Chemistry

By

Dr.

Mehnaz

Kamal

Assistant Professor,

Pharmaceutical Chemistry

Prince

Sattam

Bin

Abdulaziz

University

Slide2

WELCOME

Slide3

Amino acids

Slide4

1-To know

what is protein

2-To identify Types of

protein

3- To Know

amino acids

4-

To

differentiate between

essential and nonessential amino acids5-To understand amino acids synthesis

Slide5

Characteristics and Structures

Amino Acids

All three groups are attached to a single carbon atom called chiral carbon. There are 20 common amino acids

characterised

by different R groups.

(

Different

side chains make different amino

acids)

Amino acids are the building blocks of proteins. Each amino acid contains :1.Amino group (-NH2 group)2.Carboxyl group (-COOH group)3.R group (side chain) which determines the type of an amino acid

Slide6

Ball and stick model

Other

amino acids also exist called beta and gamma amino acids, in which the amino group is attached to the carbon which is next to α carbon called α amino

acid

The amino group is attached to the carbon atom immediately next to the carboxylate group that is α carbon, so, it is called α amino acids

Amino Acids

Slide7

α

-Amino

Acids

α

-

Amino Acids

have the amino group

α

(on

the next carbon) to the

carbonyl

group

.

a

carbon

α

-

Amino acids are classified as

neutral

,

acidic

,

basic

,

primary

, and

secondary

, depending on the

R

group.

Amino Acids

Slide8

α

-Amino

acids are

neutral

,

acidic

, or

basic

.

neutral

alanine

acidic

aspartic acid

basic

lysine

Amino Acids

Slide9

Most

α

-amino

acids are

primary

, few are

secondary

.

primary

alanine

secondary

proline

Amino Acids

Slide10

all others are optically active

(they are

chiral)

L-amino

acids are naturally occurring

absolute configuration is S

Optical Activity

Only glycine is not optically active

Amino Acids

Slide11

Zwitterions

A Zwitterion is a dipolar ion. Since amino acids contain both an

acid

and a

base

,

an internal acid-base reaction forms a

zwitterion

.

amino acid

zwitterion

Amino acids exist primarily as

zwitterions

.

Amino Acids

Slide12

Amino acid zwitterions are

amphoteric

.

They can react as either

acids

or

bases

.

In acid solution

In base solution

zwitterion

protonated

zwitterion

deprotonated

Amino Acids

Slide13

Isoelectric Points

The

isoelectric point

of an amino acid occurs at the

pH

where the amino acid exists as the

zwitterion

.

deprotonated

base solution

high pH

protonated

acid solution

low pH

zwitterion

isoelectric point

Amino Acids

Slide14

There are 20 amino acids derived from proteins.

While

there are several methods of categorizing

them.

one of the most common is to group them according to the

nature of their side chains.

1-Nonpolar Side Chains

2-Polar

, Uncharged Side Chains 3- Polar Amino Acids with Negative Charge4-Polar Amino Acids with Positive ChargeAmino Acids

Slide15

*

Phenylalanine

,

valine

, leucine, isoleucine, and methionine

(have

larger side chains and are more strongly hydrophobic).

1- Nonpolar Side Chains

*Glycine, alanine, and proline (have small, nonpolar side chains and are all weakly hydrophobic).Amino Acids There are eight amino acids with nonpolar side chains

Non Polar Amino Acids have equal number of amino and carboxyl groups and are neutral

Slide16

These amino acids do not have any charge on the 'R' group. These amino acids participate in hydrogen bonding of protein

structure

There

are also eight amino acids with polar, uncharged side chains

.

Serine and threonine

have hydroxyl groups. Asparagine and glutamine have amide groups.Histidine

and tryptophan

have heterocyclic aromatic amine side chains.Cysteine has a sulfhydryl group. Tyrosine has a phenolic side chain.2- Polar, Uncharged Side Chains Amino Acids

Slide17

Tryptophan

Slide18

*

Arginine

and

lysine

have side chains with amino groups.

3- Polar Amino Acids with Negative Charge

There are four amino acids with charged side chains.

*

Aspartic acid and glutamic acid have carboxyl groups than amino groups on their side chains making them acidicAmino Acids

more amino groups as compared to carboxyl groups making it basic

4-Polar

Amino Acids with Positive Charge

Slide19

Linear Structure

Abbreviation

Name

CH3-CH(NH2)-COOH

ala A

Alanine

HN=C(NH2)-NH-(CH2)3-CH(NH2)-COOH

arg R

Arginine

H2N-CO-CH2-CH(NH2)-COOH

asn

N

Asparagine

HOOC-CH2-CH(NH2)-COOH

asp D

Aspartic Acid

HS-CH2-CH(NH2)-COOH

cys C

Cysteine

HOOC-(CH2)2-CH(NH2)-COOH

glu E

Glutamic Acid

H2N-CO-(CH2)2-CH(NH2)-COOH

gln Q

Glutamine

NH2-CH2-COOH

gly G

Glycine

N

H-CH=N-CH=

C

-CH2-CH(NH2)-COOH

his H

Histidine

CH3-CH2-CH(CH3)-CH(NH2)-COOH

ile I

Isoleucine

Slide20

Linear Structure

Abbreviation

Name

(CH3)2-CH-CH2-CH(NH2)-COOH

leu L

Leucine

H2N-(CH2)4-CH(NH2)-COOH

lys K

Lysine

CH3-S-(CH2)2-CH(NH2)-COOH

met M

Methionine

Ph-CH2-CH(NH2)-COOH

phe F

Phenylalanine

N

H-(CH2)3-

C

H-COOH

pro P

Proline

HO-CH2-CH(NH2)-COOH

ser S

Serine

CH3-CH(OH)-CH(NH2)-COOH

thr T

Threonine

Ph

-NH-CH=

C

-CH2-CH(NH2)-COOH

trp W

Tryptophan

HO-Ph-CH2-CH(NH2)-COOH

tyr Y

Tyrosine

(CH3)2-CH-CH(NH2)-COOH

val V

Valine

Slide21

Importance of Amino Acids

Amino acids combine into small chains via chemical reactions

called

‘condensation reactions’

in which the carboxyl group and the amino group bond to one another. These small chains that contain a few amino acids linked together are called polypeptide chains (the individual amino acids are called petides).

Polypetide chains, in turn, combine into the more complex structures known as proteins Amino acids are the building blocks of protein and you get protein from your diet.

If you eat a variety of healthy protein-containing foods,

you will get all of the nine essential amino acids that your body can't make for itself.Amino Acids

Slide22

Amino acids can be found in most of the nutrients we eat. Amino acids are the building blocks of healthy protein. If the food consumed is rich in protein, our body digests the protein right down to individual amino acids and little links of amino acids is adequate to be taken over into the blood stream

Amino Acids

Slide23

There are nine amino acids that cannot be synthesized in the body. H

istidine

, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine

. We need these amino acids in specific amounts daily in our diet.

Essential

amino acids

Amino Acids

PVT

TIM

HLL

Slide24

Non Essential amino acids

Amino Acids

Seven

of them

considered conditionally essential

in the human diet, meaning their synthesis can be limited under special pathophysiological conditions, such as prematurity in the infant or individuals in severe catabolic

distress (

These

seven are arginine, cysteine, glycine, glutamine, serine, proline and tyrosine)One of 11 amino acids that are synthesized in the body and are therefore not necessary in the diet. Four amino acids are dispensable in humans, meaning they can be synthesized in the body. These four are alanine, aspartic acid, asparagine and glutamic acid.Ornithine is 21st amino acid. Pyrrolysine, sometimes considered "the 22nd amino acid", is not listed here as it is not used by humansArginine is essential for infants but not for adults.

Slide25

     

The Eleven "Nonessential" Amino Acids

Alanine    

Asparagine

Aspartate

Cysteine   

(requires sulfhydryl group from methionine)

Glutamate

Glutamine

Glycine

Proline

Serine

Tyrosine    

(synthesized from phenylalanine)

       The Nine "Essential" Amino Acids

Histidine

Isoleucine

Leucine

Lysine

Methionine

Phenylalanine

Threonine

Tryptophan

Valine

Amino Acids

Arginine 

Slide26

Amino Acids

The result is the formation of a peptide or a protein, depending upon how many amino acids there are.

Therefore, it should be possible to link amino acids together through the formation of amides.

As can be seen, the amino acids possess both functional groups required to form an amide. Each amino acid is both a carboxylic acid and an amine simultaneously

.

Slide27

Peptides are named according to the number of amino acids that are linked:

dipeptide: two amino acids

tripeptide

: three amino acids

tetrapeptide

: four amino acids

Polypeptide - < 50 amino acids

Proteins-polymers of > 50 amino acids

Peptides and Proteins

Amino Acids

Slide28

Amino Acids

Synthesis of amino acids

Strecker

amino-acid synthesis

is a series of chemical reactions that synthesize an amino acid from an aldehyde or ketone

The

aldehyde

is condensed with

ammonium chloride

in the presence of potassium cyanide to form an α-aminonitrile, which is subsequently hydrolyzed to give the desired amino-acid.

Slide29

Amino Acids

Reaction mechanism

*

In

the first part of the reaction, the

carbony

l oxygen of an aldehyde is protonated,

*followed

by

a nucleophilic attack of ammonia to the carbonyl carbon. *After subsequent proton exchange, water is cleaved from the iminium ion intermediate. *A cyanide ion then attacks the iminium carbon yielding an aminonitrile.First part

Slide30

Amino Acids

Reaction mechanism

*

the

nitrile nitrogen of the

aminonitrile is protonated, and the

nitrile carbon is attacked by a water molecule. * 1,2-diamino-diol is then formed after proton exchange and a nucleophilic attack of water to the former nitrile carbon. *Ammonia is subsequently eliminated after the protonation of the amino group, and finally the

deprotonation

of a hydroxyl group produces an

amino acid.second part

Slide31

Linkage with the life sciences

Information Enrichment

Slide32

Protein Digestion: Part 1

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Protein Digestion: Part 2

Figure 6.6

Slide34

Protein Digestion: Part 3

Figure 6.6

Slide35

Protein Digestion: Part 4

Figure 6.6

Slide36

If amino acid supply is inadequate to meet your body’s needs, a whole host of important functions can begin to suffer.This results in the appearance of signs and symptoms ranging from immune system effects to cardiovascular disease to emotional disorders and more.Typical

symptoms I see when folk are deficient in amino acids include:

•Low energy levels (even chronic fatigue)

•Depression

•Anxiety

•Memory and concentration problems•Low thyroid function (which affects everything!)•Allergic symptoms•Digestive symptoms•Inability to detoxify properly•Loss of muscle mass•Increased body fat

Possible symptoms of amino acid deficiencies and imbalances

Slide37