Thienamycin

[1] In 1976, fermentation broths obtained from the soil bacterium Streptomyces cattleya were found to be active in a screen for inhibitors of peptidoglycan biosynthesis.

[6] Unlike penicillins, which are rendered ineffective through rapid hydrolysis by the β-lactamase enzyme present in some strains of bacteria, thienamycin remains antimicrobially active.

[citation needed] The hydroxyethyl side chain of thienamycin is thought to be a result of two separate methyl transfers from S-adenosyl methionine.

How the cysteaminyl side-chain is incorporated is largely unknown, although ThnT, ThnR, and ThnH are involved in the processing of CoA to cysteamine for use in the pathway.

[citation needed] Due to low titre and to difficulties in isolating and purifying thienamycin produced by fermentation, total synthesis is the preferred method for commercial production.

The starting β-lactam for the pathway given above can be synthesized using the following method (Figure 4):[12] Since thienamycin decomposes in the presence of water, it is impractical for the clinical treatment of bacterial infections, so stable derivatives were created for medicinal consumption.

The structure of thienamycin with systematic numbering
Figure 3. Total Synthesis of (+)-Thienamycin
Figure 4. Stereoselective Formation of the Lactam Ring