Flow chemistry approaches to access norcantharidin inspired cytotoxic agents

Abstract

This project focused on the development of flow chemistry methodologies to access norcantharidin inspired analogues as potential cytotoxic agents, accessed via a convergent mixed batch-flow protocol. Within this project, an optimised flow hydrogenation protocol was established using the H-Cube Pro™ fitted with a Raney nickel CatCart® at 25 ?, full H2, and a 0.50 mL min-1 flow rate, affording norcantharidin in a quantitative conversion. Furthermore, a new flow hydrogenation protocol to cleanly effect concurrent olefin and nitrile reduction in a single flow cycle was developed using the H-Cube Pro™ fitted with a Raney cobalt CatCart® at 75 ?, 75 bar H2 pressure, full H2, and a 0.30 mL min-1 flow rate. Utilising the developed protocols, a library of six norcantharidin analogues were synthesised. Of these, a biphenyl-based derivative displayed cytotoxicity, producing an average GI50 of ? 0.04µM across a panel of eight human cancer cell lines.

Date of Award	2017
Original language	English