Synthesis of 4-substituted-3-hydroxy-5-oxo-10-oxa-4-azatricyclo[5.2.1]dec- 3-yl Acetic Acid Ethyl Esters as Norcantharidin Analogues

A novel library of eighteen 4-substituted-3-hydroxy-5-oxo-10-oxa-4-azatricyclo[5.2.1]dec-3-yl acetic acid ethyl esters was generated in high yield in two steps from norcantharidin, a known protein phosphatase 1 and 2A inhibitor that displays good anticancer activity. Interestingly these analogues are bereft of anticancer and protein phosphatase activity, but possess the attributes needed for medicinal agents and could be used as scaffolds in other targets.