Research into natural products emerged from humanity’s curiosity about the nature of matter and its role in the materia medica of diverse civilizations. Plants and fungi, in particular, supplied materials that altered behavior, perception, and well-being profoundly. Many active principles remain well-known today: strychnine, morphine, psilocybin, ephedrine. The potential to circumvent the constraints of natural supply and explore the properties of these materials led to the field of natural product synthesis. This research delivered new molecules with new properties, but also led to fundamental insights into the chemistry of the nonmetal elements H, C, N, O, P, S, Se, and their combinations, i.e., organic chemistry. It also led to a potent culture focused on bigger molecules and races to the finish line, perhaps at the expense of actionable next steps. About 20 years ago, the field began to contract in the United States. Research that focused solely on chemical reaction development, especially catalysis, filled the void. After all, new reactions and mechanistic insight could be immediately implemented by the chemistry community, so it became hard to justify the lengthy procurement of a complex molecule that sat in the freezer unused. This shift coincided with a divestment of natural product portfolios by pharmaceutical companies and an emphasis in academic organic chemistry on applications-driven research, perhaps at the expense of more fundamental science. However, as bioassays and the tools of chemical biology become widespread, synthesis finds a new and powerful ally that allows us to better deliver on the premise of the field. And the hard-won insights of complex synthesis can be better encoded digitally, mined by data science, and applied to new challenges, as chemists perturb and even surpass the properties of complex natural products. The 21st century promises powerful developments, both in fundamental organic chemistry and at the interface of synthesis and biology, if the community of scientists fosters its growth. This essay tries to contextualize natural product synthesis for a broad audience, looks ahead to its transformation in the coming years, and expects the future to be bright.

中文翻译：

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21世纪的天然产物合成：超越山顶

对天然产物的研究源于人类对物质本质及其在不同文明的药物中的作用的好奇心。尤其是植物和真菌，提供了深刻改变行为、感知和福祉的材料。许多活性成分至今仍广为人知：马钱子碱、吗啡、裸盖菇素、麻黄碱。规避天然供应限制并探索这些材料特性的潜力催生了天然产物合成领域。这项研究提供了具有新特性的新分子，同时也对非金属元素 H、C、N、O、P、S、Se 及其组合（即有机化学）的化学产生了基本的见解。它还导致了一种专注于更大分子和冲向终点线的强大文化，这或许是以牺牲可行的后续步骤为代价的。大约20年前，美国的油田开始萎缩。仅仅关注化学反应发展，特别是催化的研究填补了空白。毕竟，化学界可以立即实施新的反应和机理见解，因此很难证明长期采购未经使用的冰箱中的复杂分子是合理的。这一转变恰逢制药公司撤资天然产品组合，以及学术有机化学对应用驱动研究的重视，这或许是以牺牲更基础的科学为代价的。然而，随着生物测定和化学生物学工具的普及，合成找到了一个新的强大盟友，使我们能够在该领域更好地实现目标。随着化学家扰乱甚至超越复杂天然产物的特性，来之不易的复杂合成见解可以更好地进行数字编码，通过数据科学进行挖掘，并应用于新的挑战。如果科学家群体能够促进基础有机化学以及合成与生物学的交叉领域的发展，21 世纪必将迎来强劲的发展。本文试图为广大读者介绍天然产物合成的背景，展望未来几年的转变，并期望未来是光明的。