Department of Chemistry, University of Konstanz, 78467 Konstanz, Germany.
Science. 2020 Feb 7;367(6478):676-681. doi: 10.1126/science.aay9173.
Canataxpropellane belongs to the medicinally important taxane diterpene family. The most prominent congener, Taxol, is one of the most commonly used anticancer agent in clinics today. Canataxpropellane exhibits a taxane skeleton with three additional transannular C-C bonds, resulting in a total of six contiguous quaternary carbons, of which four are located on a cyclobutane ring. Unfortunately, isolation of canataxpropellane from natural sources is inefficient. Here, we report a total synthesis of (-)-canataxpropellane in 26 steps and 0.5% overall yield from a known intermediate corresponding to 29 steps from commercial material. The core structure of the (-)-canataxpropellane () was assembled in two steps using a Diels-Alder/-alkene-arene photocycloaddition sequence. Enantioselectivity was introduced by designing chiral siloxanes to serve as auxiliaries in the Diels-Alder reaction.
卡纳他紫杉醇属于具有重要药用价值的紫杉烷二萜类家族。其中最著名的紫杉醇是目前临床应用最广泛的抗癌药物之一。卡纳他紫杉醇具有紫杉烷骨架，还有三个额外的跨环 C-C 键，总共形成六个连续的季碳原子，其中四个位于环丁烷环上。不幸的是，从天然来源中分离卡纳他紫杉醇的效率很低。在这里，我们报道了 (-)-卡纳他紫杉醇的全合成，从已知的中间体出发，经过 26 步反应，总产率为 0.5%，而从商业原料出发则需要 29 步。(-)-卡纳他紫杉醇（）的核心结构通过 Diels-Alder/-烯烃-芳烃光环加成序列分两步组装。通过设计手性硅氧烷作为 Diels-Alder 反应的辅助剂来引入对映选择性。
