Godfrey Robert C, Jones Helen E, Green Nicholas J, Lawrence Andrew L
EaStCHEM School of Chemistry, University of Edinburgh Joseph Black Building David Brewster Road Edinburgh EH9 3FJ UK
Chem Sci. 2021 Dec 29;13(5):1313-1322. doi: 10.1039/d1sc05801k. eCollection 2022 Feb 2.
The bicyclo[2.2.2]diazaoctane alkaloids are a vast group of natural products which have been the focus of attention from the scientific community for several decades. This interest stems from their broad range of biological activities, their diverse biosynthetic origins, and their topologically complex structures, which combined make them enticing targets for chemical synthesis. In this article, full details of our synthetic studies into the chemical feasibility of a proposed network of biosynthetic pathways towards the brevianamide family of bicyclo[2.2.2]diazaoctane alkaloids are disclosed. Insights into issues of reactivity and selectivity in the biosynthesis of these structures have aided the development of a unified biomimetic synthetic strategy, which has resulted in the total synthesis of all known bicyclo[2.2.2]diazaoctane brevianamides and the anticipation of an as-yet-undiscovered congener.
双环[2.2.2]二氮杂辛烷生物碱是一大类天然产物，几十年来一直是科学界关注的焦点。这种兴趣源于它们广泛的生物活性、多样的生物合成起源以及拓扑结构复杂的特点，这些因素共同使它们成为化学合成极具吸引力的目标。在本文中，我们公开了对双环[2.2.2]二氮杂辛烷生物碱短杆菌肽酰胺家族生物合成途径拟议网络的化学可行性进行合成研究的全部细节。对这些结构生物合成中反应性和选择性问题的深入了解有助于制定统一的仿生合成策略，该策略已实现了所有已知双环[2.2.2]二氮杂辛烷短杆菌肽酰胺的全合成，并预期有一个尚未发现的同系物。
