This document discusses various types of penicillin antibiotics. It begins by introducing penicillin and its discovery by Alexander Fleming in 1929. It then classifies penicillins based on their mechanism of action, chemical structure, target organisms, and spectrum. The document goes on to describe the specific types of penicillin, including natural/fermentation derivatives like phenoxymethylpenicillin, as well as modifications that make penicillins resistant to enzymes/acid or give them an extended spectrum. It discusses the molecular structure, biosynthesis, and degradation of penicillin.

1. Antibiotics
Dr Kunal Gokhale, Dr L H Hiranandani College of Pharmacy

2. Introduction
⮚ Chemotherapy
⮚Antibiotics
⮚Classification
-Based on MOA
-Based on chemical structure
-Based on target organism
-Based on spectrum

3. Penicillin
▪Penicillium chrysogenum or Penicllium
notatum
▪β-lactum antibiotics
▪Chemically derivatives of β-lactum
dihydrothiazolidine
▪Synthetic analogues are 6-amino
penicillanic acid derivatives

4. Penicillin
• Alexander Fleming, St. Mary’s Hospital
London
1929
• Chain, Florey isolated penicillin and tested
clinical effectiveness at Oxford University
1939
E-Merck started producing penicilin, but the
use restricted.

5. Total 30 different actives were isolated at diff
centers from penicillin fungi with different
name.
Penicilin available to all after world war

6. Penicillin Nomenclature
Why β-lactum?

7. Penicillin Nomenclature
USP Nomenclature
Chemical Abstract nomenclature
4-thia-1-azabicyclo[3.2.0]heptan-7-one

8. Penicillin Nomenclature & biosynthesis
• Penam,
• Penicillanic acid
• Trivial (G,V etc)
• C3 (D),C5,C6(L) are chiral. 3S:5R:6R
• Acylamino, COOH are trans
• 6APA contain 2 amino acids: L-Cysteine &
L-Valine

9. Degradation of penicillin: Alkaline & enzymatic

10. Degradation of penicillin: Acidic
Penicillenic acid

11. Classification of penicillin
▪ Natural/Fermentation derivatives
❑ 6-Aminopenicillanic acid
❑ Pen G/Benzylpenicillin

12. Classification of penicillin
▪ Natural/Fermentation derivatives
❑ Phenoxymethylpenicillin/Pen V

13. Classification of penicillin
▪ Penicillinase/β-lactamase/ Enzyme resistant
⮚Acid labile
✔Naficillin
✔ Cloxacillin

14. Classification of penicillin
▪ Penicillinase/β-lactamase/ Enzyme resistant
⮚Acid resistant
✔Ampicillin
✔ Amoxicillin
▪ Acid resistant
✔Pen V
▪ Broad Spectrum
✔Ampicillin, Amoxicillin

15. Modifications of penicillin: Acid resistant
• Substitution of an electron withdrawing group
on α-carbon of benzyl penicillin stabilizes the
penicillin towards acid degradation
• EW group stabilizes by decreasing
nucleophilicity of carbonyl oxygen atom
towards participation in β-lactam ring
opening.
• -Cl, -NH3
+, epoxide etc.

16. Modifications of penicillin: Enzyme resistant
• Increasing steric hinderance at α-carbon of benzyl
penicillin stabilizes & increases the enzyme
resistance.
• When α-acyl C is a part of aromatic (naphthyl,
phenyl) or heteroaryl (4-isooxazolyl) activity
increases.
• Substitution on 2/o or 2,6-diortho increases steric
hinderance eg: 2,6-dimethoxyphenyl, 1-
ethoxynapthyl etc.

17. Modifications of penicillin: Enzyme resistant
• Bulkier substituents are required to confer
enzyme resistance, in case of 5 membered ring
heterocycles.
• Isooxazolyl penicillins with EN groups in 3 phenyl
gp. are resistant to acid catalyzed hydrolysis of β-
lactam.

18. Modifications of penicillin: Extended spectrum
• Introduction of ionized or polar gp. on α-carbon
makes the compound active against Gm-ve
bacteria.α-OH increases spectrum.
• Acidic substituent on α-carbon makes the
compound polar making penetration of such
compounds through porins of Gm-ve bacteria easy.
Eg. Carbenicillin, –COOH containing compound
forms zwitterion.
• α-uredio penicillins are also active. Eg: Pipericillin.

19. MOA