Abstract

Acid-ester and acid-amide norcantharidin derivatives are prepared using a ‘one-pot’ synthetic procedure utilizing the ThalesNano H-cube™ flow hydrogenator. Traditionally, rapid library generation and reaction scale up of these analogues was limited by the batch wise hydrogenation of 5,6-dehydronorcantharidin. This was resolved with the use of flow chemistry. With no associated scale up issues, a method was devised to produce norcantharidin, along with acid-ester and acid-amide analogues on any scale necessary for biological screening.

Keywords: Cantharidin, Norcantharidin, Flow hydrogenation, Flow chemistry, Protein phosphatase inhibition, anti-malarial, anti-parasitic, Diels, –, Alder, Parr hydrogenation, H-cube, Kinomics, acetone, acid ester, nucleophilicity