Question

What is the principal precursor of the semi-synthetic penicillins, how is it produced and why is it suitable for the generation of the semi-synthetic compounds?

Answer 1

Answer with discussion and explanation :

Penicillins are the earliest recognised antibiotics derived naturally from Peinicillium molds. Alexander Fleming is credited for the discovery of penicillin which revolutionised treatment approach to infections by bacteria.

Penicillins have a beta lactam ring which binds with penicillin binding protein to inhibit cell wall synthesis and thus kills bacteria. These naturally occurring penicillins showed very good effects against Gram positive bacteria, but showed less activity against Gram negative bacteria.

To improve its spectrum and other properties certain changes were made artificially/chemically to produce new penicillins which have better spectrum termed as semisynthetic penicillins such as Ampicillin and amoxicillin.

6- Aminopenicillanic acid ( 6-APA) serves as the precursor for the synthesis of semisynthetic penicillins because it has carboxylic acid group which determines its binding to penicillin binding protein of bacteria. Hydrogen of amino group can be replaced by the different side chains by transamidation giving many different derived semisynthetic penicillins giving them required spectrum or properties. Thus 6-APA is the suitable precursor which retains penicillin binding activity and also allows for different side chains addition giving rise to different semisynthetic penicillins.

For synthesis of semisynthetic penicillin, naturally obtained penicillin (penicillin G) is hydrolysed by acylase to obtain 6-APA (precursor) and then by transamidation different side chains are added at amino group producing different semisynthetic penicillins.