This document discusses macrolide antibiotics. It begins by introducing macrolides as a class of antibiotics characterized by their large lactone ring structures. It then classifies macrolides based on their ring size and discusses key macrolides like erythromycin. The document outlines the chemistry of macrolides, including their characteristic lactone ring, ketone/hydroxyl groups, and deoxy sugar components. It also discusses the structural activity relationship of macrolides using erythromycin as a lead compound and how derivatives like clarithromycin, roxithromycin and azithromycin were developed for improved properties.

1. MACROLIDE
ANTIBIOTICS
Submitted to:- Submitted by:-
Dr. Om Silakari Karan Dutt
M Pharmacy
18301122

2. CONTENT
 INTRODUCTION
 CLASSIFICATION
 CHEMISTRY
 STRUCTURAL ACTIVITY RELATIONSHIP
 LEAD OPIMIZATION

3. MACROLIDE ANTIBIOTICS
 Macrolide, class of antibiotics characterized by their
large lactone ring structures and by their growth-inhibiting
(bacteriostatic) effects on bacteria.
 Antibiotics isolated from the Actinomycetes is the group of
chemically related compounds called the Macrolides.
 In 1950, Picromycin, the first of this group to be identified as a
macrolide compound, was first reported.
 In 1952, erythromycin and carbomycin were reported as new
antibiotics.
 1970s and 1980s synthetic derivatives of erythromycin,
including Clarithromycin and Azithromycin, were developed.

4. Macrolides are protein synthesis inhibitors Macrolide antibiotics do so
by binding reversibly to the P site on the 50S subunit of the
bacterial ribosome and by preventing peptidyltransferase from adding
the growing peptide attached to tRNA to the next amino acid as well
as inhibiting ribosomal translation.
It may be bacteriostatic or bactericidal depending on concentration
Classification of macrolide antibiotic
1. 14-Membered ring -
A. Natural – Erythromycin etc.
B. Semi synthetic - Roxithromycin, Clarithromycin
2. 15- Membered ring-
A. Semi synthetic – Azithromycin.
3. 16-Membered ring –
A. Natural – Josamycin, spiramycin
B. Semi- synthetic – Miokamycin, Rokitamycin

5. STRUCTURE OF MACROLIDE ANTIBIOTIC
Erythromycin A Clarithromycin Roxithromycin

6. CHEMISTRY OF MACROLIDE
ANTIBIOTIC
 Macrolide antibiotic
Contain three characteristic part
in every molecule,
1.A marcocyclic lactone ring
Contain 14-16 carbon usually.
2.Mutiple ketone group
Or hydroxyl group
3.Deoxy sugar attached
to lactone ring by glycosidic
linkage
General structure of macrolide antibiotic

7. ERYTHROMYCIN A
Replaced C12-OH group with H atom forms more acid
stable Erythromycin A than Erythromycin.

8. ERYTHROMYCIN C
Cladinose –OCH3 replaced with -OH
The C analog differs from erythromycin by the replacement of the
methoxyl group on the cladinose moiety with a hydrogen atom. It
appears to be as active as erythromycin but is present in very small
amounts in fermentation liquors.

9. SAR OF MACROLIDES
Erythromycin

10. SAR OF MACROLIDES
 A lactone ring, a ketone group, and a amino sugar are
the basic characterstic group that are present in a
macrolide and are desired for activity.
 The amino sugar present must be glycosidically
bonded.
 Lactone ring contains 12,14,16 atomsmust in cyclic
ring along with olephinic group and hence called
macrolides.
 Neutral sugar are present in addition to glycosidically
bonded sugar.
 Dimethyl amino group provide basic properties to
macrolides

11. ERYTHROMYCIN AS A LEAD COMPOUND

12. 1. When C6 hydroxy group in erythromycin has been
converted to an methoxy. E,g claritromycin. The
spectrum is slightly improved compared to
erythromycin (but less active),Greater acid stability
than erythromycin, Does not cause cramp in GIT -
Higher blood concentrations. More lipophilicity,
Longer half-life.
2. The addition of hydroxylamine to the ketone to form
oxime. Increased acid stability by reducing
intermolecular ketalization

13. LEAD COMPOUNDS
Clarithromycin Roxithromycin

14. 3. Nitrogen atom has been introduced to expand a 14- membered
ring to 15-membered azalide ring (azithromycin). Removal of
the 9-keto group coupled with incorporation of a weakly basic
tertiary amine nitrogen function into the macrolide ring
increases the stability.
 Azithromycin (Zithromax) is a semisynthetic derivative of
erythromycin, prepared by Beckman rearrangement of the
corresponding oxime, followed by N methylation and
reduction of the resulting ring-expanded lactam.
azithromycin

15.  It is a prototype of a series of nitrogen-containing, 15-
membered ring macrolides known as azalides. Removal
of the 9-keto group coupled with incorporation of a
weakly basic tertiary amine nitrogen function into the
macrolide ring increases the stability of azithromycin to
acid-catalyzed degradation

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