Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis.
Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis.
复制标题
鏻盐/路易斯酸中继催化不对称合成N-桥[3.3.1]环体系
DOI：
10.1038/s41467-022-28001-8
复制
发表时间：
2022-01-18
影响因子：
16.6
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Tan JP;Li K;Shen B;Zhuang C;Liu Z;Xiao K;Yu P;Yi B;Ren X;Wang T
光学纯的伪天然产物(PNP)，特别是氮杂二环[3.3.1]壬烷分子及其类似物，为研究结构−活性关系提供了一个诱人的平台，也引领了药物开发中新的化合物发现。然而，目前还没有指导催化不对称策略来构建如此重要的PN-支架的例子，因此限制了它们的广泛应用。在这里，我们报道了一种通用的模块化方法，通过级联工艺在双功能膦盐/Lewis酸接力催化下构建了这些拟天然的N-桥联[3.3.1]环体系。具有各种官能团的多种底物(59例)与该方案兼容。其他特点包括[3 + 2]环化/开环/傅立叶-克拉夫茨级联反应，优异的反应性和立体选择性，易于获得的起始原料，步骤经济性和可扩展性。所得对映体富集物具有初步的抗癌活性。我们的研究成果有望推动催化合成具有挑战性的手性PNPs，为生物活性小分子的发现提供新的机会。含N-桥联[3.3.1]环系统的光学纯伪天然产物(PNP)为研究结构−活性关系提供了一个平台，但目前还没有催化不对称策略来构建这种支架。在这里，作者展示了通过双功能膦盐/Lewis酸接力催化来构建这种N-桥联[3.3.1]环体系的一般方法。
Optically pure pseudo-natural products (PNPs), particularly exemplified by azabicyclo[3.3.1]nonane molecules and their analogs provide an attractive platform for structure−activity relationship studies, and also lead new compound discovery in drug development. However, there are currently no examples of guiding catalytic asymmetric strategies available to construct such important PN-scaffolds, thus limiting their broad use. Here, we report a general and modular method for constructing these pseudo-natural N-bridged [3.3.1] ring systems via cascade process by bifunctional phosphonium salt/Lewis acid relay catalysis. A wide variety of substrates bearing an assortment of functional groups (59 examples) are compatible with this protocol. Other features include a [3 + 2] cyclization/ring-opening/Friedel-Crafts cascade pathway, excellent reactivities and stereoselectivities, easily available starting materials, step economy and scalability. The obtained enantioenriched products showed potential of preliminary anticancer activities. Insights gained from our studies are expected to advance general efforts towards the catalytic synthesis of challenging even unprecedented chiral PNPs, offering new opportunities for bioactive small-molecule discovery. Optically pure pseudo-natural products (PNPs) bearing N-bridged [3.3.1] ring systerm provide a platform for structure−activity relationship studies, but currently no examples of catalytic asymmetric strategies are available to construct such scaffolds. Here the authors show a general method for constructing such N-bridged [3.3.1] ring systems via a bifunctional phosphonium salt/Lewis acid relay catalysis.
登录
查看更多内容
影响因子：
16.6
作者：
Edwankar, Chitra R.;Edwankar, Rahul V.;Deschamps, Jeffrey R.;Cook, James M.
通讯作者：
Cook, James M.
影响因子：
4.3
作者：
Rebmann, Heiko;Gerlinger, Christa K. G.;Gaich, Tanja
通讯作者：
Gaich, Tanja
影响因子：
3.6
作者：
Neipp, CE;Martin, SF
通讯作者：
Martin, SF
来自含有大环内林或肉毒杆菌单元的双旋核生物碱的合成：综述。
DOI：
10.3390/molecules21111525
发表时间：
2016-11-14
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Rahman MT;Tiruveedhula VV;Cook JM
通讯作者：
Cook JM
影响因子：
16.6
作者：
Noeren-Mueller, Andrea;Wilk, Wolfram;Waldmann, Herbert
通讯作者：
Waldmann, Herbert