Kadaník Michal, Frantsuzova Ekaterina, Matouš Petr, Nováková Lucie, Kuneš Jiří, Bonsignore Manola, Andris Erik, Růžičková Zdeňka, Pour Milan
Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
Org Lett. 2024 Dec 20;26(50):11080-11084. doi: 10.1021/acs.orglett.4c04378. Epub 2024 Dec 7.
The first total syntheses of the natural isocoumarin prunolactone A with a 6/6/6/6/6 spiropentacyclic skeleton and its unnatural (3')-epimer in 10 and 8 steps, respectively, are reported. The syntheses feature generation of a reactive 3,4-bis(methylene)isocoumarin intermediate, its biomimetic Diels-Alder reactions with the shikimic-acid-derived scytolide and (8)-scytolide, and a Mitsunobu reaction allowing access to scytolide in a stereochemically pure form. Computational support for the selectivity of the Diels-Alder reaction is provided.
报道了具有6/6/6/6/6螺五环骨架的天然异香豆素李属内酯A及其非天然（3'）-差向异构体分别经10步和8步的首次全合成。合成过程的特点包括生成一个活性3,4-双（亚甲基）异香豆素中间体、其与源自莽草酸的scytolide和（8）-scytolide的仿生狄尔斯-阿尔德反应，以及一个能以立体化学纯形式获得scytolide的光延反应。提供了狄尔斯-阿尔德反应选择性的计算支持。
