Synthesis of cytotoxic spirocyclic imides from a biomass-derived oxanorbornene

Stefan B. Lawrenson, Amanda K. Pearce, Sam Hart, Adrian C. Whitwood, Rachel K. O'Reilly, Michael North*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


N-Substituted derivatives of cantharimide and norcantharimide represent a promising but underutilized motif for therapeutic applications. Herein, we report a divergent strategy for the preparation of secondary amides and norcantharimide-resembling spirocyclic imides from a biomass-derived oxanorbornene and assess their biological activity. Computational modelling suggests these compounds fall perfectly within lead-like chemical space (200 Da < RMM < 350 Da, −1 < AlogP < 3), with the spirocyclic imides preferred due to their lack of reactive functionalities. Biological analysis of the spirocyclic imides revealed that the compounds displayed antiproliferative activity against a range of human cancer cells (A549, HCT 116, OVCAR-3, MDA-MB-231, MCF7 and PC-3) with the N-octyl derivative displaying the greatest potential as a potent broad-spectrum anticancer drug. Dose-response curves for the N-octyl spirocyclic imide found EC50 values of 56–95 μM dependent on the cell line, with highest activity against human colorectal carcinoma cells (HCT 116).

Original languageEnglish
Article number131754
Publication statusAccepted/In press - 2020

Bibliographical note

Funding Information:
SL would like to thank the EPSRC (grant number EP/M506680/1 ) and BP plc for financial support. The authors would like to thank the European Research Council for funding (grant number 615142 ).

Publisher Copyright:
© 2020 Elsevier Ltd

Copyright 2020 Elsevier B.V., All rights reserved.


  • Active surfactants
  • Cantharidin
  • Cytotoxicity
  • Drug design
  • Spirocyclic

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry


Dive into the research topics of 'Synthesis of cytotoxic spirocyclic imides from a biomass-derived oxanorbornene'. Together they form a unique fingerprint.

Cite this