Pharmaceutical Organic Chemistry

1. Pharmaceutical Organic Chemistry By Dr. MehnazKamal Assistant Professor, Pharmaceutical Chemistry Prince Sattam Bin Abdulaziz University

2. WELCOME

3. Amino acids

4. 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 acids 5-To understand amino acids synthesis

5. Amino Acids Characteristics and Structures Amino acids are the building blocks of proteins. Each amino acid contains : 1.Amino group (-NH2group) 2.Carboxyl group (-COOH group) 3.R group (side chain) which determines the type of an amino acid 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)

6. Amino Acids Ball and stick model 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 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

7. a carbon Amino Acids α-Amino Acids α -Amino Acids have the amino group α(on the next carbon) to the carbonylgroup. α -Amino acids are classified as neutral, acidic, basic, primary, and secondary, depending on the R group.

8. Amino Acids α-Amino acids are neutral,acidic, or basic. acidic aspartic acid basic lysine neutral alanine

9. Amino Acids Most α-amino acids are primary, few are secondary. primary alanine secondary proline

10. Amino Acids Optical Activity • Only glycine is not optically active all others are optically active (they are chiral) • L-amino acids are naturally occurring • absolute configuration is S

11. Amino Acids Zwitterions A Zwitterion is a dipolar ion. Since amino acids contain both anacidand abase, an internal acid-base reaction forms azwitterion. amino acid zwitterion Amino acids exist primarily as zwitterions.

12. Amino Acids Amino acid zwitterions are amphoteric. They can react as either acids or bases. In acid solution zwitterion protonated In base solution zwitterion deprotonated

13. Amino Acids Isoelectric Points The isoelectric pointof an amino acid occurs at the pH where the amino acid exists as the zwitterion. deprotonated base solution high pH zwitterion isoelectric point protonated acid solution low pH

14. Amino Acids 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 Charge • 4-Polar Amino Acids with Positive Charge

15. Amino Acids • 1- Nonpolar Side Chains Non Polar Amino Acids have equal number of amino and carboxyl groups and are neutral There are eight amino acids with nonpolar side chains • *Glycine, alanine, and proline • (have small, nonpolar side chains and are all weakly hydrophobic). * Phenylalanine, valine, leucine, isoleucine, and methionine (have larger side chains and are more strongly hydrophobic).

16. Amino Acids • 2- Polar, Uncharged Side Chains 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. Tyrosinehas a phenolic side chain.

17. Tryptophan

18. Amino Acids There are four amino acids with charged side chains. • 3- Polar Amino Acids with Negative Charge • *Aspartic acid and glutamic acid • have carboxyl groups than amino groups on their side chains making them acidic 4-Polar Amino Acids with Positive Charge more amino groups as compared to carboxyl groups making it basic *Arginine and lysinehave side chains with amino groups.

21. Amino Acids Importance of Amino Acids 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 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). Polypetidechains, in turn, combine into the more complex structures known as proteins

22. Amino Acids 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

23. Amino Acids Essential amino acids There arenine amino acids that cannot be synthesized in the body. Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. We need these amino acids in specific amounts daily in our diet. PVT TIM HLL

24. Amino Acids Non Essential amino acids One of 11 amino acids that are synthesized in the body and are therefore not necessary in the diet. Sevenof 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) Arginine is essential for infants but not for adults. Fouramino 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 humans

25. Amino Acids Arginine 

26. Amino Acids • 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. • Therefore, it should be possible to link amino acids together through the formation of amides. The result is the formation of a peptide or a protein, depending upon how many amino acids there are.

27. Amino Acids Peptides and Proteins • 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

28. 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.

29. Amino Acids Reaction mechanism First part *In the first part of the reaction, the carbonyl 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 ionintermediate. *A cyanide ion then attacks the iminium carbon yielding an aminonitrile.

30. Amino Acids Reaction mechanism second part *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.

31. Linkage with the life sciences Information Enrichment

32. Protein Digestion: Part 1

33. Protein Digestion: Part 2 Figure 6.6

34. Protein Digestion: Part 3 Figure 6.6

35. Protein Digestion: Part 4 Figure 6.6

36. Possible symptoms of amino acid deficiencies and imbalances 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