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