The development of antibiotic resistance in bacteria means that there is an ongoing demand for new antibacterial agents. Platencin, which was first isolated in 2007, shows activity against a broad range of bacteria including the drug-resistant strains MRSA (methicillin-resistant Staphylococcus aureus) and VRE (vancomycin resistant enterococci). Synthetic routes that enable easy access to platencin and closely related structures are therefore important in the fight against infection. The importance of platencin is illustrated by the fact that two total syntheses and one formal synthesis have already been reported in 2008.

Now, two research groups have independently reported further new approaches to the formal synthesis of platencin. Both routes provide access to a key bicyclic ketone, and each relies on a diastereoselective cycloaddition reaction. Nicolaou, Toh and Chen, from the Institute of Chemical and Engineering Sciences in Singapore, use1 an intramolecular Diels–Alder reaction to create the bicyclic structure, the stereoselectivity of which is controlled by a chiral allylic alcohol introduced earlier through an enantioselective reduction. Meanwhile, Rutjes and co-workers, from Radboud University Nijmegen, the Netherlands, opted2 for a chiral-pool strategy, and used high pressure conditions to achieve an otherwise unfavourable intermolecular Diels–Alder reaction with the readily available and inexpensive (S)-(–)-perillaldehyde.

Both routes provide an efficient and rapid synthesis of platencin that may be used in their own right, but equally may be applied in the discovery of related structures that could show significant antibacterial activity.