Synthesis of many different types of organic small molecules using one automated process.
Synthesis of many different types of organic small molecules using one automated process.
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DOI：
10.1126/science.aaa5414
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发表时间：
2015-03-13
期刊：
影响因子：
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通讯作者：
Burke MD
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文献类型：
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作者：
Li J;Ballmer SG;Gillis EP;Fujii S;Schmidt MJ;Palazzolo AM;Lehmann JW;Morehouse GF;Burke MD
小分子合成通常依赖于针对每个靶点高度定制的程序。一个广泛适用的自动化过程可以大大增加这类化合物的可及性，使其实际潜力的调查。在这里，我们报告了14个不同类别的小分子的合成使用相同的全自动化过程。这是通过战略性地扩展基于构建块的合成平台的范围以包括甚至富含Csp3的多环天然产物框架并发现适用于所有相应中间体的捕获和释放色谱纯化方案来实现的。由于已有数千种兼容的构建模块可用于商业用途，许多小分子现在可以通过该平台获得。更广泛地说，这些发现为小分子合成提供了一个更通用和自动化的可行路线图。
Small molecule synthesis usually relies on procedures highly customized for each target. A broadly applicable automated process could greatly increase the accessibility of this class of compounds to enable investigations of their practical potential. Here we report the synthesis of 14 distinct classes of small molecules using the same fully automated process. This was achieved by strategically expanding the scope of a building block-based synthesis platform to include even Csp3-rich polycyclic natural product frameworks and discovering a catch-and-release chromatographic purification protocol applicable to all of the corresponding intermediates. With thousands of compatible building blocks already commercially available, many small molecules are now accessible with this platform. More broadly, these findings illuminate an actionable roadmap to a more general and automated approach for small molecule synthesis.