Total Synthesis

A major focus of our program is on the total synthesis of structurally complex natural products. We are particularly interested in targets that exhibit rich stereochemical features and potentially useful biological activity. Examples of ongoing total synthesis targets include eribulin (analogue of the natural product halichondrin B and approved drug for metastatic breast cancer) and the potent marine cytotoxic agent eleutherobin. We have also disclosed the synthesis of key fragments of phormidolide A, a toxic metabolite of the cyanobacterium Phormidium sp., including a stereochemical reassignment of the natural product with Professor Ian Paterson (Cambridge). Examples of recently completed natural products, as well as current targets are depicted in the slideshow on the left.

Highlighted Works:

  • Britton, R., et al. 'Synthetic Transformations of Eleutherobin Reveal New Features of Its Microtubule-Stabalizing Pharmacophore' JACS., 2001

  • Halperin, S. and Britton, R. 'Chlorine, an atom economical auxiliary for asymmetric aldol reactions' Org. Biomol. Chem., 2013

  • Holmes, M. and Britton, R. 'Total Synthesis and Structural Revision of Laurefurenynes A and B' Chem. Euro. J., 2013

  • Dhand, V., et al. 'A Short, Organocatalytic Formal Synthesis of (-)-Swainsonine and Related Alkaloids' Chem. Euro. J., 2015

  • Chang, S., et al. 'Total Synthesis and Configurational Assignment of Ascospiroketal A' Chem. Euro. J., 2015

  • Chang, S., et al. 'Total Synthesis of Ascospiroketal A Through a Ag(I)-Promoted Cyclization Cascade' Angew. Chem. Int. Ed., 2015

  • Holmes, M., et al. 'Total Synthesis of Amphirionin-4' Org. Lett., 2015

  • Meanwell, M., et al. 'Application of Sequential Proline-catalyzed α-chlorination and Aldol Reactions in the Total Synthesis of 1-deoxygalactonojirimycin' Can. J. Chem., 2017

  • Lam, N., et al. 'A Counterintuitive Stereochemical Outcome from a Chelation-controlled Vinylmetal Aldehyde Addition Leads to the Configurational Reassignment of Phormidolide A' Chem. Commun., 2019

  • Challa, V.R., et al. 'Total synthesis of biselide A' Chem. Sci., 2021

  • Kaghad, A., et al. 'An α-chloroaldehyde-based formal synthesis of eribulin' Nat. Commun., 2023

    Darryl M. Wilson and Robert Britton. 'Enantioselective Total Synthesis of the Marine Macrolides Salarins A and C' Journal of the American Chemical Society, 2024