Total synthesis of brevianamide A
Total synthesis of brevianamide A
复制标题
DOI：
10.1038/s41557-020-0442-3
复制
发表时间：
2020-04-13
期刊：
影响因子：
21.8
通讯作者：
Lawrence, Andrew L.
中科院分区：
文献类型：
--
作者：
Godfrey, Robert C.;Green, Nicholas J.;Lawrence, Andrew L.
真菌衍生的双环[2.2.2]二氮杂辛烷生物碱因其有效和多样的生物活性而引起科学界的兴趣。在这一庞大而多样的天然产物家族中，杀虫代谢物（+）-短藤酰胺A因其难以合成和无法解释的生物成因而特别值得注意。尽管经过了五十年的研究，这种生物碱仍然是化学合成的一个难以捉摸的目标，这是由于与所有以前探索的策略相关的反应性和选择性的不可逾越的问题。我们在此报道了（+）-灯盏花素酰胺A的化学合成（七步，7.2%总产率，750 mg规模），其涉及线性稠合的（-）-脱氢灯盏花素酰胺E到拓扑复杂的桥连螺稠合结构的（+）-灯盏花素酰胺A的生物启发级联转化。
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.