Suppr超能文献

21世纪的天然产物合成:超越巅峰。

Natural Product Synthesis in the 21st Century: Beyond the Mountain Top.

作者信息

Shenvi Ryan A

机构信息

Department of Chemistry, Scripps Research, La Jolla, California 92037, United States.

Graduate School of Chemical and Biological Sciences, Scripps Research, La Jolla, California 92037, United States.

出版信息

ACS Cent Sci. 2024 Feb 14;10(3):519-528. doi: 10.1021/acscentsci.3c01518. eCollection 2024 Mar 27.

Abstract

Research into natural products emerged from humanity's curiosity about the nature of matter and its role in the 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.

摘要

对天然产物的研究源于人类对物质本质及其在不同文明中的作用的好奇。特别是植物和真菌,提供了能深刻改变行为、感知和健康状况的物质。许多活性成分如今依然广为人知:士的宁、吗啡、裸盖菇素、麻黄碱。规避天然供应限制并探索这些物质特性的潜力催生了天然产物合成领域。这项研究带来了具有新特性的新分子,但也引发了对非金属元素氢、碳、氮、氧、磷、硫、硒及其组合(即有机化学)化学性质的深入洞察。它还催生了一种专注于更大分子的强大文化,并引发了冲向终点线的竞赛,或许是以牺牲可行的后续步骤为代价。大约20年前,该领域在美国开始萎缩。专注于化学反应开发,尤其是催化的研究填补了这一空白。毕竟,新反应和机理洞见能立即被化学界应用,因此很难为冷藏库中闲置的复杂分子的漫长采购流程找到正当理由。这一转变恰逢制药公司剥离天然产物产品线,以及学术有机化学强调应用驱动的研究,或许是以牺牲更基础的科学为代价。然而,随着生物测定和化学生物学工具的广泛应用,合成找到了一个新的强大盟友,使我们能够更好地实现该领域的前提。而且复杂合成中来之不易的洞见能够更好地进行数字编码,由数据科学挖掘,并应用于新的挑战,因为化学家们干扰甚至超越了复杂天然产物的特性。如果科学界推动其发展,21世纪有望在基础有机化学以及合成与生物学的交叉领域取得重大进展。本文试图为广大读者梳理天然产物合成的背景,展望其在未来几年的转变,并期待光明的未来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c8/10979479/964bdb65ffe6/oc3c01518_0001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验