Lindel Thomas
TU Braunschweig, Institute of Organic Chemistry, Braunschweig, Germany.
Alkaloids Chem Biol. 2017;77:117-219. doi: 10.1016/bs.alkal.2016.12.001. Epub 2017 Jan 20.
More than a decade after our last review on the chemistry of the pyrrole-imidazole alkaloids, it was time to analyze once more the developments in that field. The comprehensive article focusses on the total syntheses of pyrrole-imidazole alkaloids that have appeared since 2005. The classic monomeric pyrrole-imidazole alkaloids have all been synthesized, sometimes primarily to demonstrate the usefulness of a new method, as in the case of the related molecules agelastatin A and cyclooroidin with more than 15 syntheses altogether. The phakellin skeleton has been made more than 10 times, too, with a focus on the target structure itself. Thus, some of the pyrrole-imidazole alkaloids are now available in gram amounts, and the supply problem has been solved. The total synthesis of the dimeric pyrrole-imidazole alkaloids is still mostly in its pioneering phase with two routes to palau'amine and massadine discovered and three routes to the axinellamines and ageliferin. In addition, the review summarizes recent discoveries regarding the biological activity of the pyrrole-imidazole alkaloids. Regarding the biosynthesis of sceptrin, a pathway is proposed that starts from nagelamide I and proceeds via two electrocyclizations and reduction.
在我们上次对吡咯 - 咪唑生物碱化学的综述过去十多年后，是时候再次分析该领域的进展了。这篇综述文章聚焦于自2005年以来出现的吡咯 - 咪唑生物碱的全合成。经典的单体吡咯 - 咪唑生物碱均已被合成，有时主要是为了证明一种新方法的实用性，比如相关分子agelastatin A和环海鞘素，总共已有超过15种合成方法。法可林骨架也已被合成了10多次，重点在于目标结构本身。因此，现在一些吡咯 - 咪唑生物碱能够以克级规模获得，供应问题已得到解决。二聚体吡咯 - 咪唑生物碱的全合成大多仍处于开创性阶段，已发现两条合成帕劳胺和马萨丁的路线，以及三条合成轴索胺和海鞘素的路线。此外，该综述总结了关于吡咯 - 咪唑生物碱生物活性的近期发现。关于司克菌素的生物合成，提出了一条从纳格拉酰胺I开始，经两次电环化和还原的途径。
