A Collection of Robust Organic Synthesis Reactions for In Silico Molecule Design

A focused collection of organic synthesis reactions for computer-based molecule construction is presented. It is inspired by real-world chemistry and has been compiled in close collaboration with medicinal chemists to achieve high practical relevance. Virtual molecules assembled from existing starting material connected by these reactions are supposed to have an enhanced chance to be amenable to real chemical synthesis. About 50% of the reactions in the dataset are ring-forming reactions, which fosters the assembly of novel ring systems and innovative chemotypes. A comparison with a recent survey of the reactions used in early drug discovery revealed considerable overlaps with the collection presented here. The dataset is available encoded as computer-readable Reaction SMARTS expressions from the Supporting Information presented for this paper.本文呈现了一组聚焦于计算机辅助分子构建的有机合成反应数据集。其灵感源自真实化学实践，并与药物化学家紧密协作完成编纂，以保障极高的实际应用价值。通过该类反应连接现有起始原料构建的虚拟分子，其可经真实化学合成手段制备的概率显著提升。本数据集内约50%的反应为成环反应，有助于构建新型环系与创新化学型。通过与近期一项针对早期药物发现中所用反应的调研对比可知，本数据集与该调研中的反应集合存在大量重合。本数据集以计算机可读的反应SMARTS（Reaction SMARTS）编码格式，可从本文的支撑材料中获取。