Hetzler Belinda E, Trauner Dirk, Lawrence Andrew L
Department of Chemistry, New York University, New York, NY, USA.
EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh, UK.
Nat Rev Chem. 2022 Mar;6(3):170-181. doi: 10.1038/s41570-021-00345-7. Epub 2022 Jan 14.
Natural product synthesis remains one of the most vibrant and intellectually rewarding areas of chemistry, although the justifications for pursuing it have evolved over time. In the early years, the emphasis lay on structure elucidation and confirmation through synthesis, as exemplified by celebrated studies on cocaine, morphine, strychnine and chlorophyll. This was followed by a phase where the sheer demonstration that highly complex molecules could be recreated in the laboratory in a rational manner was enough to justify the economic expense and intellectual agonies of a synthesis. Since then, syntheses of natural products have served as platforms for the demonstration of elegant strategies, for inventing new methodology 'on the fly' or to demonstrate the usefulness and scope of methods established with simpler molecules. We now add another aspect that we find fascinating, viz. 'natural product anticipation'. In this Review, we survey cases where the synthesis of a compound in the laboratory has preceded its isolation from nature. The focus of our Review lies on examples where this anticipation of a natural product has triggered a successful search or where synthesis and isolation have occurred independently. Finally, we highlight cases where a potential natural product structure has been suggested as a result of synthetic endeavours but not yet confirmed by isolation, inviting further collaborations between synthetic and natural product chemists.
天然产物合成仍然是化学领域中最具活力和智力回报最高的领域之一，尽管追求它的理由随着时间的推移而有所演变。在早期，重点在于通过合成来阐明和确证结构，例如对可卡因、吗啡、士的宁和叶绿素的著名研究。随后进入了一个阶段，仅仅证明高度复杂的分子能够在实验室中以合理的方式重新合成，就足以证明合成所需的经济成本和智力投入是合理的。从那时起，天然产物的合成一直作为展示精妙策略的平台，用于即时发明新方法，或展示用较简单分子建立的方法的实用性和适用范围。我们现在又增加了一个我们觉得很有吸引力的方面，即“天然产物预测”。在本综述中，我们考察了在实验室中合成一种化合物先于其从自然界中分离出来的案例。我们综述的重点在于这样的例子，即这种对天然产物的预测引发了成功的寻找，或者合成与分离是独立进行的。最后，我们强调了一些案例，其中由于合成工作而提出了潜在的天然产物结构，但尚未通过分离得到证实，这促使合成化学家和天然产物化学家之间展开进一步的合作。
