Whereas most organic molecules can be synthesized from progressively simpler substrates, syntheses of complex organic targets often involve counterintuitive sequence of steps that first complexify the structure but, by doing so, open up possibilities for pronounced structural simplification in subsequent, downstream steps. Such complexifying/simplifying reaction sequences, called tactical combinations (TCs), can be quite powerful and elegant but also inherently hard to spot—indeed, only some 500 TCs have so far been cataloged, and even fewer are routinely used in synthetic practice. This paper describes computer-driven discovery of large numbers of viable TCs (over 46,000 combinations of reaction classes and ∼4.85 million combinations of reaction variants), the vast majority of which have no prior literature precedent. Examples—including a concise wet lab synthesis of a small natural product—are provided to illustrate how the use of these newly discovered TCs can streamline the design of syntheses leading to important drugs and/or natural products.

尽管大多数有机分子可以从逐步简化的底物上合成，但是复杂有机靶标的合成通常涉及反直观的步骤顺序，这些步骤首先使结构复杂化，但这样做却为后续后续步骤的结构简化提供了可能。这种复杂化/简化的反应序列，称为战术组合（TC），功能强大而优雅，但固有地也难以发现-实际上，到目前为止，仅分类了约500个TC，而在合成实践中常规使用的数量甚至更少。本文描述了计算机驱动的大量TC的发现（超过46,000个反应类别的组合和约485万个反应变体的组合），其中绝大多数没有现有文献先例。