Synthetic chemistry has traditionally relied on reactions between reactants of high chemical potential and transformations that proceed energetically downhill to either a global or local minimum (thermodynamic or kinetic control). Catalysts can be used to manipulate kinetic control, lowering activation energies to influence reaction outcomes. However, such chemistry is still constrained by the shape of one-dimensional reaction coordinates. Coupling synthesis to an orthogonal energy input can allow ratcheting of chemical reaction outcomes, reminiscent of the ways that molecular machines ratchet random thermal motion to bias conformational dynamics. This fundamentally distinct approach to synthesis allows multi-dimensional potential energy surfaces to be navigated, enabling reaction outcomes that cannot be achieved under conventional kinetic or thermodynamic control. In this Review, we discuss how ratcheted synthesis is ubiquitous throughout biology and consider how chemists might harness ratchet mechanisms to accelerate catalysis, drive chemical reactions uphill and programme complex reaction sequences.

传统上，合成化学依赖于高化学势的反应物之间的反应和转化，这些反应大力下降到全局或局部最小值（热力学或动力学控制）。催化剂可用于操纵动力学控制，降低活化能以影响反应结果。然而，这种化学仍然受到一维反应坐标形状的限制。将合成与正交能量输入耦合可以使化学反应结果产生棘轮，这让人想起分子机器棘轮随机热运动以偏置构象动力学的方式。这种根本上不同的合成方法允许导航多维势能表面，从而实现传统动力学或热力学控制下无法实现的反应结果。在这篇综述中，我们讨论了棘轮合成如何在整个生物学中普遍存在，并考虑化学家如何利用棘轮机制来加速催化，推动化学反应上升并编程复杂的反应序列。