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. 2020 Jul;12(7):615-619.
doi: 10.1038/s41557-020-0442-3. Epub 2020 Apr 13.

Total synthesis of brevianamide A

Robert C Godfrey  1 , Nicholas J Green  1 , Gary S Nichol  1 , Andrew L Lawrence  2
Affiliations

Total synthesis of brevianamide A

Robert C Godfrey et al. Nat Chem. 2020 Jul.

Abstract

The fungal-derived bicyclo[2.2.2]diazaoctane alkaloids are of interest to the scientific community for their potent and varied biological activities. Within this large and diverse family of natural products, the insecticidal metabolite (+)-brevianamide A is particularly noteworthy for its synthetic intractability and inexplicable biogenesis. Despite five decades of research, this alkaloid has remained an elusive target for chemical synthesis due to insurmountable issues of reactivity and selectivity associated with all previously explored strategies. We herein report the chemical synthesis of (+)-brevianamide A (seven steps, 7.2% overall yield, 750 mg scale), which involves a bioinspired cascade transformation of the linearly fused (-)-dehydrobrevianamide E into the topologically complex bridged-spiro-fused structure of (+)-brevianamide A.

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