Flagstad Thomas, Hansen Mette R, Le Quement Sebastian T, Givskov Michael, Nielsen Thomas E
Department of Chemistry, Technical University of Denmark , DK-2800 Kgs. Lyngby, Denmark.
ACS Comb Sci. 2015 Jan 12;17(1):19-23. doi: 10.1021/co500091f. Epub 2014 Dec 17.
A build/couple/pair strategy for the synthesis of complex and densely functionalized small molecules is presented. The strategy relies on synthetically tractable building blocks (build), that is, diversely substituted hydrazides, α-hydroxy aldehydes, and boronic acids, which undergo Petasis 3-component reactions (couple) to afford densely functionalized anti-hydrazido alcohols. The resulting scaffolds can subsequently be converted via chemoselective cyclization reactions (pair), including intramolecular Diels-Alder or Ru-alkylidene catalyzed ring-closing metathesis, into sets of structurally diverse heterocycles in good yields in only 3-4 steps.
本文提出了一种用于合成复杂且功能密集型小分子的构建/偶联/配对策略。该策略依赖于易于合成的构建模块（构建），即各种取代的酰肼、α-羟基醛和硼酸，它们通过Petasis三组分反应（偶联）生成功能密集型抗酰肼醇。所得的支架随后可通过化学选择性环化反应（配对）进行转化，包括分子内狄尔斯-阿尔德反应或钌亚烷基催化的闭环复分解反应，仅需3至4步就能以良好的产率转化为一系列结构多样的杂环化合物。
