Ray Sayan, Mondal Subhajit, Mukherjee Santanu
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
Angew Chem Int Ed Engl. 2022 Jun 13;61(24):e202201584. doi: 10.1002/anie.202201584. Epub 2022 Apr 12.
Ladderane phospholipids, with their unusual ladder-like arrangement of concatenated cyclobutane rings, represent an architecturally unique class of natural products. However, despite their fascinating structure and other necessary impetus, only a few synthetic studies of these molecules have been reported so far. We have now devised a concise total synthesis of [3]-ladderanol, a component of natural ladderane phospholipids, using an organocatalytic enantioselective desymmetrizing formal C(sp )-H alkylation. Our synthetic strategy rests on the late-stage introduction of chirality, thus allowing facile access to both enantiomers of [3]-ladderanol as well as an analogue. This is the first time a desymmetrization strategy is applied to the synthesis of [3]-ladderanol. The scope of this desymmetrizing C(sp )-H alkylation of meso-cyclobutane-fused cyclohexenediones is also presented.
梯形烷磷脂具有独特的由多个稠合环丁烷环组成的阶梯状排列结构，是一类在结构上独一无二的天然产物。然而，尽管它们具有迷人的结构以及其他诸多推动因素，但迄今为止，关于这些分子的合成研究报道却很少。我们现在设计了一种简洁的全合成方法来制备天然梯形烷磷脂的一种成分——[3]-梯形醇，该方法采用了有机催化对映选择性去对称化形式的C(sp³)-H烷基化反应。我们的合成策略基于手性的后期引入，从而能够轻松获得[3]-梯形醇的两种对映体以及一种类似物。这是首次将去对称化策略应用于[3]-梯形醇的合成。本文还展示了这种内消旋环丁烷稠合环己二烯酮的去对称化C(sp³)-H烷基化反应的适用范围。
