Nanomole-scale high-throughput chemistry for the synthesis of complex molecules
Nanomole-scale high-throughput chemistry for the synthesis of complex molecules
复制标题
DOI：
10.1126/science.1259203
复制
发表时间：
2015-01-02
期刊：
影响因子：
56.9
通讯作者：
Dreher, Spencer D.
中科院分区：
文献类型：
--
作者：
Santanilla, Alexander Buitrago;Regalado, Erik L.;Dreher, Spencer D.
在新的合成努力的最前沿，如药物发现或天然产物合成，大量的材料很少可用，时间表很紧。一个小型化的自动化平台，使高通量实验的合成路线侦察，以确定条件的制备反应规模扩大将是一个变革性的进步。由于自动化、小型化的化学在固体或挥发性有机溶剂存在下难以进行，因此大多数合成“工具包”不能容易地小型化。使用钯催化的交叉偶联反应作为测试案例，我们开发了在室温下在二甲基亚砜中运行的自动化友好反应。这一进展使我们能够将生物技术中使用的机器人技术与新兴的基于质谱的高通量分析技术结合起来。在不到一天的时间里进行了1500多个化学实验，每次反应仅使用0.02毫克的材料。
At the forefront of new synthetic endeavors, such as drug discovery or natural product synthesis, large quantities of material are rarely available and timelines are tight. A miniaturized automation platform enabling high-throughput experimentation for synthetic route scouting to identify conditions for preparative reaction scale-up would be a transformative advance. Because automated, miniaturized chemistry is difficult to carry out in the presence of solids or volatile organic solvents, most of the synthetic "toolkit" cannot be readily miniaturized. Using palladium-catalyzed cross-coupling reactions as a test case, we developed automation-friendly reactions to run in dimethyl sulfoxide at room temperature. This advance enabled us to couple the robotics used in biotechnology with emerging mass spectrometry-based high-throughput analysis techniques. More than 1500 chemistry experiments were carried out in less than a day, using as little as 0.02 milligrams of material per reaction.