Structure – Activity Relationship of Penicillins
Session 26: Structure – Activity Relationship of Penicillins.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Penicillins |
| | |Presentation | |
|3 |40 minutes |Presentation |Chemical Structure of Penicilins |
|4 |45 minutes |Group |Structure – Activity Relationship of|
| | |discussion |Penicillins |
| | |Presentation | |
|5 |10 minutes |Presentation |Key Points |
| 6 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Penicillins (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are penicillins? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the table below |
inhibiting ell wall synthesis.
penicillins and semisynthetic penicillins.
are mainly active against gram (+) ve bacteria.
STEP 3: Chemical Structure of Penicillins (40 minutes).
Fig. 24.1 General Chemical structure of penicillin
[pic]
G.L Patrick, an introduction to medical chemistry.
consisting of a four membered β-lactam ring fused to a five-membered
thiazolidine ring.
amino acids cysteine and valine. According to biogenesis, antibiotics
can be derived from various natural substances like β-lactam
antibiotics from cysteine and valine amino acids.
[pic]
Penicillin appears to be derived from
cysteine and valine
[pic]
Side chain varies according to carboxylic acids presents in
fermentation medium.
[pic]
that contains three chiral centers.
active forms.
activity, has the stereochemistry of 3S:5R:6R. (According to BP & USP
2S:5R:6R).
[pic]
Penicillin analogues
[pic]
STEP 4: Structure – Activity relationship of Penicillins (45 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question. |
|What is the importance of structure activity relationship of |
|Penicillins? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
A large number of penicillin analogues have been synthesized and studied.
The results of these studies have demonstrated following features are
important for penicillins activity.
side-chain is important.
Very little variation is possible in penicillin nucleus.
Structure activity relationships of penicillin
[pic]
The acid sensitivity of penicillin.
There are three reasons for the acid sensitivity of penicillin.
o The bicyclic system in penicillin consists of a four-membered ring and
a five membered ring.
o As a result, penicillins suffers large angle and torsional strains.
o Acid-catalyzed ring opening relieves these strains by breaking open
the more highlystrained four-memberedβ-lactam ring.
[pic]
[pic]
Ring opening
o The carbonyl group in the β-lactam ring is highly susceptible to
nucleophiles and it does not behave like a normal tertiary amide which
is usually quite resistant to nucleophilic attack.
o A normal tertiary amide is far less susceptible to nucleophiles since
the resonance structures reduce the electrophilic character of the
carbonyl group.
o The β-lactam nitrogen is unable to show such effect.
o To show the similar effect like tertiary amide, penicillin had to
obtain astrained flat structure, which is highly unstable.
o As a result, the lone pair is localized on the nitrogen atom and the
carbonyl group is far more electrophilic than a tertiary amide.
[pic]
o Figure above demonstrates how the neighboring acyl group canactively
participate in a mechanism to open up the lactam ring.
o Thus,penicillin Ghas a self-destruct mechanism built into its
structure.
[pic]
Influence of the acyl side chain on acid sentivity
[pic]
STEP 5: Key Points (10 minutes).
molds of genus Penicillium and also semi-synthetically, having a
bactericidal action on many susceptible Gram positive and Gram-
negative bacteria.
negative cocciand bacilli, some also being effective against certain sp
irochetes.
member of the penicillins which has the molecular formula R-
C9H11N2O4S, where R is the variable side chain that differentiates the
penicillins from one another.
such as ampicillin, improving their spectrum of activity and
bioavailability (amoxicillin), development of beta-lactamase resistant
drugs, (oxacillin, cloxacillin), and broad spectrum penicillins
(Carbenicillin, ureidopenicillins)
STEP 6: Evaluation (10 minutes)
penicillins?
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
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