Researchers in the UK have made progress towards the synthesis of tagetitoxin, a naturally occurring compound that inhibits RNA polymerase. 

Julien Plet and Michael Porter at University College London have constructed what they say is the unusual bicyclic core of the highly functionalised molecule tagetitoxin. This compound was first isolated from a bacterium in 1981, and has never been synthesised.

 Tagetitoxin inhibits the enzyme RNA polymerase, which produces RNA from a DNA template, in plant and animal cells. 'The unique biological activity of tagetitoxin is a bonus, as it gives us another justification for making it, beyond the sheer chemical challenge,' said Porter.

 

       

 

The researchers started their synthesis from a sugar derivative, and constructed the bridge of the bicyclic intermediate by unmasking a thiol in the presence of a ketone group. This triggered spontaneous cyclisation. The structure of the resulting compound was confirmed by mass spectrometry and NMR spectroscopy. 

Porter's goal is the total synthesis of tagetitoxin, so that the biology of the compound can be explored. Installing the functional groups 'will likely present the biggest challenge in completing the synthesis,' he said. 

David Barden