REVISITING THE STRUCTURE OF STRYCHNINE AND RELATED COMPOUNDS: AN “INADEQUATE” APPROACH TO WOODWARD AND ROBINSON’S WORK.

Abstract

Background: The structural elucidation of strychnine and brucine by Woodward and Robinson is a landmark in natural products chemistry. At the time it was done by classic degradation techniques.

Aims: This research was taken place to confirm and advance the findings of original work by innovative scientists such as Woodward and Robinson via modern analysis. As well as investigating older structure elucidation techniques to determine which method has the largest impact on degrading complex alkaloids such as strychnine and brucine, we will apply these compounds to modern NMR experiments such as INADEQUATE.

Methods: a range of degradation techniques such as base hydrolysis, amination, dehydrogenation and oxidation reactions were reproduced and monitored with modern instruments such as EI-LC MS and NMR to deduce structural insights surrounding strychnine’s degradant products. The modern equipment was also used to further current data surrounding strychnine via running elaborate 2D NMR procedures such as 13C-13C INADEQUATE.

Results: dehydrogenation via bromination and sulfonation had the greatest influence on degrading strychnine. NMR experiments revealed molecular relationships between the carbons to be able to piece together the skeletal backbone of the compound. 

Conclusion: Overall, the development in modern analysis has been a key turning point in structure determination, further degradations would be running paired with more extensive 2D NMR processes and older methods are effective but are much more beneficial when hybridised with new technology.