Chloramphenicol (SAR & Synthesis included)

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Chemical Structure / Formula of Chloramphenicol

• Formula: C11H12Cl2N2O5

• Structure: Contains a nitrobenzene ring, a dichloroacetamide group, and a hydroxylated propanediol moiety.

Mechanism of Action

• Binds to the 50S ribosomal subunit, inhibiting peptidyl transferase activity and preventing peptide bond formation.

• Bacteriostatic at low doses but bactericidal against some bacteria (e.g., Haemophilus influenzae, Neisseria meningitidis).

Uses

• Meningitis (alternative in β-lactam allergy): H. influenzae, N. meningitidis, S. pneumoniae.

• Rickettsial infections (Rocky Mountain spotted fever) in patients who cannot take tetracyclines.

• Serious anaerobic infections (e.g., Bacteroides fragilis).

Side Effects

• Bone marrow suppression (dose-dependent, reversible).

• Aplastic anemia (idiosyncratic, irreversible, fatal).

• Gray baby syndrome (accumulation in neonates due to immature UDP-glucuronyl transferase).

• GI upset, peripheral neuropathy (long-term use).

Structure-Activity Relationship (SAR) of Chloramphenicol

Structural Feature	Role in Activity
p-Nitro group on benzene ring	Essential for antibacterial activity. Reduction or substitution leads to loss of activity.
D-threo isomer (natural configuration)	Only this stereoisomer is active; the erythro form is much less active.
Alcohol group (-OH) on side chain	Required for proper binding to ribosomal subunit.
Dichloroacetyl moiety	Crucial for activity. Modifications usually reduce antibacterial effect.
Amide linkage	Maintains orientation of the side chain for effective binding.

Synthesis of Chloramphenicol

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