Failed experiment by Cambridge scientists leads to surprise drug development breakthrough
剑桥科学家一次失败的实验意外促成药物研发突破
An unexpected result during a routine control test in Cambridge revealed a new light-powered chemical reaction that could make drug manufacturing more sustainable. It could also give scientists better tools to improve existing medicines and develop new ones.
剑桥大学在一次常规对照实验中出现的意外结果，揭示了一种新型光驱动化学反应，有望使药物制造更加可持续。该发现还可为科学家提供更优工具，用于改进现有药物并开发新药。
Peer-Reviewed Publication
经同行评审发表
St. John's College, University of Cambridge
剑桥大学圣约翰学院
Scientists at the University of Cambridge have developed a new way to alter complex drug molecules using light rather than toxic chemicals – a discovery that could accelerate and improve how medicines are designed and made.
剑桥大学的科学家开发出一种新方法：利用光而非有毒化学品来修饰复杂的药物分子——这一发现有望加速并改进药物的设计与制造流程。
Published today (Thursday 12 March) in Nature Synthesis, the study introduces what the team calls an “anti-Friedel–Crafts” reaction.
该研究于今日（2026年3月12日，星期四）发表于《自然·合成》（Nature Synthesis），研究团队将其称为“反傅-克反应”（anti-Friedel–Crafts reaction）。
A classic Friedel–Crafts reaction uses strong chemicals or metal catalysts under harsh experimental conditions. This means the reaction can only happen in the early stages of drug manufacturing, and is followed by many additional chemical steps to produce the final drug.
传统的傅-克反应需在苛刻实验条件下使用强腐蚀性化学品或金属催化剂，因此只能在药物制造的早期阶段进行，之后还需经过大量额外化学步骤才能得到最终药物。
The new Cambridge approach reverses that pattern, allowing scientists to modify drug molecules at the final stages of production.
而剑桥大学的新方法则颠覆了这一模式，使科学家能够在生产流程的最（后）阶段对药物分子进行修饰。
Rather than relying on heavy metal catalysts, the chemistry is powered by an LED lamp at ambient temperature. When activated, it triggers a self-sustaining chain process that forges new carbon–carbon bonds under mild conditions and without toxic or expensive chemicals.
该反应不依赖重金属催化剂，而是由常温下的LED灯驱动。一旦启动，便会触发一个自持链式反应，在温和条件下形成新的碳–碳键，且无需有毒或昂贵的化学试剂。
In practical terms, this means chemists can make targeted changes late in the development of a new or existing drug rather than dismantling and rebuilding complex molecules from scratch – a process that can otherwise take months.
从实际角度看，这意味着化学家可以在新药或现有药物研发的后期进行精准修改，而不必从头拆解并重建复杂分子——后者通常耗时数月。
“We’ve found a new way to make precise changes to complex drug molecules, particularly ones that have been exceptionally difficult to modify in the past,” said David Vahey, first author and a PhD researcher at St John’s College, Cambridge.
论文作者、剑桥大学圣约翰学院博士研究员大卫·韦希（David Vahey）表示：“我们找到了一种新方法，可对复杂药物分子进行准确确修饰，尤其是那些过去极难改造的分子。”
“Scientists can spend months rebuilding large parts of a molecule just to test one small change. Now, instead of doing a multistep process for hundreds of molecules, scientists can start with their hit and make small modifications later on.”
“科学家可能花数月时间重建分子的大部分结构，只为测试一处微小改动。现在，他们无需对数百个分子逐一进行多步合成，而是可以直接从‘命中化合物’（hit）出发，在后期进行小幅修饰。”
“This reaction lets scientists make precise adjustments much later in the process, under mild conditions and without relying on toxic or expensive reagents. That opens chemical space that has been hard to access before and gives medicinal chemists a cleaner, more efficient tool for exploring new versions of a drug.”
“这一反应让科学家能在流程后期、温和条件下、不依赖有毒或昂贵试剂的情况下进行精准调整。这打开了此前难以触及的化学空间，为药物化学家提供了更清洁、高效的工具，用于探索药物的新版本。”
Fewer steps mean fewer chemicals, less energy consumption, a smaller environmental footprint and significant time savings for chemists. This highly selective reaction lets scientists make precise adjustments much later in the process. That matters enormously in drug development, where even a minor structural tweak can significantly affect how well a medicine works, how it behaves in the body, or how many side effects it causes.
步骤减少意味着化学品用量更少、能耗更低、环境足迹更小，并为化学家节省大量时间。这种高选择性反应使科学家能在研发后期进行精准调整——这在药物开发中至关重要，因为即使微小的结构改动也可能显著影响药效、体内代谢行为或副作用数量。
The Cambridge breakthrough tackles one of the most fundamental steps in that process: forming carbon–carbon bonds, the links that underpin everything from fuels to complex biomolecules.
剑桥大学的突破针对的是药物合成中最基础的步骤之一：构建碳–碳键——这是从燃料到复杂生物分子的核心连接。
The method is highly selective, meaning it can alter one part of a molecule without disturbing other sensitive regions – what chemists call “high functional-group tolerance”. That makes it particularly suited to late-stage optimisation – a key part of modern medicinal chemistry, where scientists fine-tune molecules to improve how drugs perform.
该方法具有高度选择性，即能修饰分子中的特定部位而不干扰其他敏感区域——化学家称之为“高官能团耐受性”。这使其特别适用于“后期优化”（late-stage optimisation），即现代药物化学中科学家精细调整分子以提升药物性能的关键环节。
By avoiding heavy metal catalysts, hazardous conditions and reducing the need for long synthetic sequences, the reaction could also dramatically cut toxic chemical waste and energy use in pharmaceutical development, which is an increasing priority as the industry seeks to reduce its environmental footprint.
通过避免使用重金属催化剂和危险条件，并减少对长合成序列的需求，该反应还能大幅削减制药研发中的有毒化学废物和能源消耗——随着行业致力于降低环境影响，这一点正变得日益重要。
Vahey is a member of Professor Erwin Reisner’s research group at Cambridge. Reisner’s group is known for developing systems inspired by photosynthesis, using sunlight to convert certain types of waste, water and the greenhouse gas carbon dioxide into useful chemicals and fuels.
韦希是剑桥大学埃尔温·赖斯纳（Erwin Reisner）教授研究组成员。该团队以开发仿光合作用系统著称，利用阳光将某些废弃物、水和温室气体二氧化碳转化为有用的化学品和燃料。
Reisner, Professor of Energy and Sustainability in the Yusuf Hamied Department of Chemistry, lead author of the paper, said the importance of the latest work lies in expanding what chemists can do under practical conditions while developing greener manufacturing methods.
赖斯纳是化学系尤素夫·哈米德能源与可持续发展讲席教授，也是本文通讯作者。他表示，这项（最）新）工作的重要性在于：在实用条件下拓展了化学家的能力边界，同时推动更绿色的制造方法。
“This is a new way to make a fundamental carbon–carbon bond and that’s why the potential impact is so great. It also means chemists can avoid an undesirable and inefficient drug modification process.”
“这是一种构建基础碳–碳键的新方法，正因如此，其潜在影响才如此巨大。这也意味着化学家可以避开一种不理想且低效的药物修饰流程。”
The team demonstrated the reaction across a wide range of drug-like molecules and showed it could be adapted to continuous-flow systems increasingly used in industry. Collaboration with AstraZeneca helped test whether the method could meet the practical and environmental demands of large-scale pharmaceutical development.
研究团队在多种类药分子上验证了该反应，并证明其可适配工业界日益采用的连续流（continuous-flow）系统。与阿斯利康（AstraZeneca）的合作帮助测试了该方法能否满足大规模药物开发的实际与环保需求。
“Transitioning the chemical industry to a sustainable industry is arguably one of the most difficult parts of the whole energy transition,” explained Reisner.
赖斯纳解释道：“推动化工行业向可持续转型，可以说是整个能源转型中最困难的部分之一。”
And the breakthrough came from a laboratory setback – like some of science’s most famous discoveries, from X-rays and penicillin to Viagra and modern weight-loss drugs.
而这一突破恰恰源于一次实验室挫折——正如科学史上许多重大发现一样，从X射线、青霉素到伟哥（Viagra）和现代减肥药皆是如此。
“Failure after failure, then we found something we weren’t expecting in the mess – a real diamond in the rough. And it is all thanks to a failed control experiment,” Vahey said.
韦希说：“经历了一次又一次失败后，我们在混乱中发现了一个意想不到的东西——一颗真正的璞玉。这一切都要归功于一次失败的对照实验。”
He had been testing a photocatalyst when he removed it as part of a control test and found the reaction worked just as well, and in some cases better, without it.
他当时正在测试一种光催化剂，作为对照实验的一部分将其移除，却发现反应在没有它的情况下依然有效，甚至在某些情况下效果更好。
At first, the unusual product appeared to be a mistake. Instead of discarding it, the team decided to understand what it meant.
起初，这种异常产物看似是个错误。但团队没有将其丢弃，而是决定弄清其背后的意义。
Reisner said the breakthrough depended not just on chemistry, but on judgement.
赖斯纳表示，这一突破不仅依赖化学，更依赖判断力。
“Recognising the value in the unexpected is probably one of the key characteristics of a successful scientist,” he said.
他说：“认识到意外发现的价值，或许正是成功科学家的关键特质之一。”
“We generate enormous amounts of data, and increasingly we use artificial intelligence to help analyse it. We have an algorithm that can predict reactivity. AI helps because we don’t need chemists to do endless trial and error, but an algorithm will only follow the rules it has been given. It still takes a human being to look at something that appears wrong and ask whether it might actually be something new.”
“我们产生了海量数据，越来越多地借助人工智能进行分析。我们有一个能预测反应活性的算法。AI的作用在于避免化学家陷入无休止的试错，但算法只会遵循既定规则。仍需人类去审视那些看似错误的结果，并思考它是否可能代表某种新事物。”
In this case, it was Vahey who recognised its significance and investigated further.
这一次，正是韦希意识到了其重要性并深入探究。
“David could have dismissed it as a failed control,” Reisner said. “Instead, he stopped and thought about what he was seeing. That moment, choosing to investigate rather than ignore it, is where discovery happens.”
赖斯纳说：“大卫本可以把它当作一次失败的对照实验而忽略。但他停下来思考自己看到的现象。正是在选择探究而非忽视的那个瞬间，发现诞生了。”
Once the team had mapped the underlying chemistry, they brought in machine-learning models – developed in collaboration with Trinity College Dublin – to predict where the reaction would occur on entirely new molecules that had never been tested in the lab.
一旦团队厘清了背后的化学机理，便引入了与都柏林三一学院合作开发的机器学习模型，用于预测该反应在从未在实验室测试过的新分子上的发生位置。
By learning the patterns from established chemistry, AI could effectively simulate reactions before they were run, helping researchers identify the most promising candidates faster and with far less trial and error. The result is a tool that doesn't just work in the lab but could actively help scientists develop new drugs more quickly in the future.
通过学习已知化学反应的规律，AI可在实验前有效模拟反应，帮助研究人员更快识别最有前景的候选分子，大幅减少试错。其成果不仅是一个实验室工具，未来还可能主动助力科学家加速新药研发。
For Vahey, it’s providing researchers with a vital new tool in the toolbox of drug discovery and development.
对韦希而言，这为药物发现与开发的研究人员提供了一件至关重要的新工具。
He said: “What industry and other researchers do with it next – that’s where the future impact lies. For us, the lab is mostly average to bad days. The good days are very good days.”
他说：“业界和其他研究人员接下来如何运用它——那才是未来影响力所在。对我们来说，实验室的日子大多是平庸甚至糟糕的。但好日子一旦到来，就格外美好。”
Reisner added: “As a chemist, you only need one or two good days a year – and those can come from a failed experiment.”
赖斯纳补充道：“作为一名化学家，你一年只需一两个好日子——而这些好日子，往往就来自一次失败的实验。”
Reference
参考文献
David Vahey et al, Anti-Friedel–Crafts alkylation via electron donor–acceptor photoinitiation, Nature Synthesis. DOI 10.1038/s44160-026-00994-w.
David Vahey 等，《基于电子给体–受体光引发的反傅-克烷基化反应》，《自然·合成》，DOI: 10.1038/s44160-026-00994-w。
【科学发现侧栏】10项（著）名的意外科学发现
[Side Panel] 10 Famous Accidental Scientific Discoveries
- X射线（1895年）：威廉·康拉德·伦琴在研究玻璃管中的电流时，意外发现附近屏幕发光，从而揭示了一种能透视人体内部的新辐射。
- 放射性（1898年）：玛丽·居里发现某些铀矿石的辐射远超纯铀所能解释，由此发现了钋和镭，奠定核物理与化学基础。
- 硫化橡胶（1839年）：查尔斯·固特异意外将橡胶与硫磺混合物洒在热炉上，未熔化反而变得坚韧有弹性，催生了轮胎等工业应用。
- 青霉素（1928年）：亚历山大·弗莱明发现霉菌污染的培养皿中细菌被杀死，由此诞生首（个）广泛应用的抗生素。
- 特氟龙（1938年）：罗伊·普朗凯特在制冷剂实验中意外合成出极其光滑耐热的材料，后用于不粘锅。
- 超级胶（1942年）：哈里·库弗试图开发透明塑料时，意外得到一种瞬间强力粘合剂。
- LSD（1943年）：阿尔伯特·霍夫曼意外吸收自己合成的化合物，体验到强烈致幻效果，后成为神经科学研究工具。
- 脉冲星（1967年）：乔丝琳·贝尔·伯内尔在分析射电望远镜数据时发现规律脉冲信号，实为快速旋转的中子星。
- 伟哥（1990年代）：辉瑞公司测试心绞痛药物时，受试者报告意外“坚挺”副作用，后开发为治疗勃起功能障碍药物。
- 减肥注射剂（2021年）：研究2型糖尿病新药时发现GLP-1类似物可显著减重，催生Ozempic、Mounjaro等肥胖治疗药物。
原文链接：https://www.eurekalert.org/news-releases/1119254
本文通过A!翻译。
