Failed experiment by Cambridge scientists leads to surprise drug development breakthrough
劍橋科學家一次失敗的實驗意外促成藥物研發突破
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.
劍橋大學在一次常規對照實驗中出現的意外結果，揭示了一種新型光驅動化學反應，有望使藥物制造更加可持續。該發現還可為科學家提供更優工具，用于改進現有藥物并開發新藥。
Peer-Reviewed Publication
經同行評審發表
St. John's College, University of Cambridge
劍橋大學圣約翰學院
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.
劍橋大學的科學家開發出一種新方法：利用光而非有毒化學品來修飾復雜的藥物分子——這一發現有望加速并改進藥物的設計與制造流程。
Published today (Thursday 12 March) in Nature Synthesis, the study introduces what the team calls an “anti-Friedel–Crafts” reaction.
該研究于今日（2026年3月12日，星期四）發表于《自然·合成》（Nature Synthesis），研究團隊將其稱為“反傅-克反應”（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.
傳統的傅-克反應需在苛刻實驗條件下使用強腐蝕性化學品或金屬催化劑，因此只能在藥物制造的早期階段進行，之后還需經過大量額外化學步驟才能得到最終藥物。
The new Cambridge approach reverses that pattern, allowing scientists to modify drug molecules at the final stages of production.
而劍橋大學的新方法則顛覆了這一模式，使科學家能夠在生產流程的最（后）階段對藥物分子進行修飾。
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.
該反應不依賴重金屬催化劑，而是由常溫下的LED燈驅動。一旦啟動，便會觸發一個自持鏈式反應，在溫和條件下形成新的碳–碳鍵，且無需有毒或昂貴的化學試劑。
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.
從實際角度看，這意味著化學家可以在新藥或現有藥物研發的后期進行精準修改，而不必從頭拆解并重建復雜分子——后者通常耗時數月。
“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.
論文作者、劍橋大學圣約翰學院博士研究員大衛·韋希（David Vahey）表示：“我們找到了一種新方法，可對復雜藥物分子進行準確確修飾，尤其是那些過去極難改造的分子。”
“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.”
“科學家可能花數月時間重建分子的大部分結構，只為測試一處微小改動。現在，他們無需對數百個分子逐一進行多步合成，而是可以直接從‘命中化合物’（hit）出發，在后期進行小幅修飾。”
“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.”
“這一反應讓科學家能在流程后期、溫和條件下、不依賴有毒或昂貴試劑的情況下進行精準調整。這打開了此前難以觸及的化學空間，為藥物化學家提供了更清潔、高效的工具，用于探索藥物的新版本。”
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.
步驟減少意味著化學品用量更少、能耗更低、環境足跡更小，并為化學家節省大量時間。這種高選擇性反應使科學家能在研發后期進行精準調整——這在藥物開發中至關重要，因為即使微小的結構改動也可能顯著影響藥效、體內代謝行為或副作用數量。
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.
劍橋大學的突破針對的是藥物合成中最基礎的步驟之一：構建碳–碳鍵——這是從燃料到復雜生物分子的核心連接。
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.
該方法具有高度選擇性，即能修飾分子中的特定部位而不干擾其他敏感區域——化學家稱之為“高官能團耐受性”。這使其特別適用于“后期優化”（late-stage optimisation），即現代藥物化學中科學家精細調整分子以提升藥物性能的關鍵環節。
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.
通過避免使用重金屬催化劑和危險條件，并減少對長合成序列的需求，該反應還能大幅削減制藥研發中的有毒化學廢物和能源消耗——隨著行業致力于降低環境影響，這一點正變得日益重要。
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.
韋希是劍橋大學埃爾溫·賴斯納（Erwin Reisner）教授研究組成員。該團隊以開發仿光合作用系統著稱，利用陽光將某些廢棄物、水和溫室氣體二氧化碳轉化為有用的化學品和燃料。
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.
賴斯納是化學系尤素夫·哈米德能源與可持續發展講席教授，也是本文通訊作者。他表示，這項（最）新）工作的重要性在于：在實用條件下拓展了化學家的能力邊界，同時推動更綠色的制造方法。
“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.”
“這是一種構建基礎碳–碳鍵的新方法，正因如此，其潛在影響才如此巨大。這也意味著化學家可以避開一種不理想且低效的藥物修飾流程。”
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.
研究團隊在多種類藥分子上驗證了該反應，并證明其可適配工業界日益采用的連續流（continuous-flow）系統。與阿斯利康（AstraZeneca）的合作幫助測試了該方法能否滿足大規模藥物開發的實際與環保需求。
“Transitioning the chemical industry to a sustainable industry is arguably one of the most difficult parts of the whole energy transition,” explained Reisner.
賴斯納解釋道：“推動化工行業向可持續轉型，可以說是整個能源轉型中最困難的部分之一。”
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.
而這一突破恰恰源于一次實驗室挫折——正如科學史上許多重大發現一樣，從X射線、青霉素到偉哥（Viagra）和現代減肥藥皆是如此。
“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.
韋希說：“經歷了一次又一次失敗后，我們在混亂中發現了一個意想不到的東西——一顆真正的璞玉。這一切都要歸功于一次失敗的對照實驗。”
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.
他當時正在測試一種光催化劑，作為對照實驗的一部分將其移除，卻發現反應在沒有它的情況下依然有效，甚至在某些情況下效果更好。
At first, the unusual product appeared to be a mistake. Instead of discarding it, the team decided to understand what it meant.
起初，這種異常產物看似是個錯誤。但團隊沒有將其丟棄，而是決定弄清其背后的意義。
Reisner said the breakthrough depended not just on chemistry, but on judgement.
賴斯納表示，這一突破不僅依賴化學，更依賴判斷力。
“Recognising the value in the unexpected is probably one of the key characteristics of a successful scientist,” he said.
他說：“認識到意外發現的價值，或許正是成功科學家的關鍵特質之一。”
“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.”
“我們產生了海量數據，越來越多地借助人工智能進行分析。我們有一個能預測反應活性的算法。AI的作用在于避免化學家陷入無休止的試錯，但算法只會遵循既定規則。仍需人類去審視那些看似錯誤的結果，并思考它是否可能代表某種新事物。”
In this case, it was Vahey who recognised its significance and investigated further.
這一次，正是韋希意識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.”
賴斯納說：“大衛本可以把它當作一次失敗的對照實驗而忽略。但他停下來思考自己看到的現象。正是在選擇探究而非忽視的那個瞬間，發現誕生了。”
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.
一旦團隊厘清了背后的化學機理，便引入了與都柏林三一學院合作開發的機器學習模型，用于預測該反應在從未在實驗室測試過的新分子上的發生位置。
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.
通過學習已知化學反應的規律，AI可在實驗前有效模擬反應，幫助研究人員更快識別最有前景的候選分子，大幅減少試錯。其成果不僅是一個實驗室工具，未來還可能主動助力科學家加速新藥研發。
For Vahey, it’s providing researchers with a vital new tool in the toolbox of drug discovery and development.
對韋希而言，這為藥物發現與開發的研究人員提供了一件至關重要的新工具。
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.”
他說：“業界和其他研究人員接下來如何運用它——那才是未來影響力所在。對我們來說，實驗室的日子大多是平庸甚至糟糕的。但好日子一旦到來，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.”
賴斯納補充道：“作為一名化學家，你一年只需一兩個好日子——而這些好日子，往往就來自一次失敗的實驗。”
Reference
參考文獻
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，《基于電子給體–受體光引發的反傅-克烷基化反應》，《自然·合成》，DOI: 10.1038/s44160-026-00994-w。
【科學發現側欄】10項（著）名的意外科學發現
[Side Panel] 10 Famous Accidental Scientific Discoveries
- X射線（1895年）：威廉·康拉德·倫琴在研究玻璃管中的電流時，意外發現附近屏幕發光，從而揭示了一種能透視人體內部的新輻射。
- 放射性（1898年）：瑪麗·居里發現某些鈾礦石的輻射遠超純鈾所能解釋，由此發現了釙和鐳，奠定核物理與化學基礎。
- 硫化橡膠（1839年）：查爾斯·固特異意外將橡膠與硫磺混合物灑在熱爐上，未熔化反而變得堅韌有彈性，催生了輪胎等工業應用。
- 青霉素（1928年）：亞歷山大·弗萊明發現霉菌污染的培養皿中細菌被殺死，由此誕生首（個）廣泛應用的抗生素。
- 特氟龍（1938年）：羅伊·普朗凱特在制冷劑實驗中意外合成出極其光滑耐熱的材料，后用于不粘鍋。
- 超級膠（1942年）：哈里·庫弗試圖開發透明塑料時，意外得到一種瞬間強力粘合劑。
- LSD（1943年）：阿爾伯特·霍夫曼意外吸收自己合成的化合物，體驗到強烈致幻效果，后成為神經科學研究工具。
- 脈沖星（1967年）：喬絲琳·貝爾·伯內爾在分析射電望遠鏡數據時發現規律脈沖信號，實為快速旋轉的中子星。
- 偉哥（1990年代）：輝瑞公司測試心絞痛藥物時，受試者報告意外“堅挺”副作用，后開發為治療勃起功能障礙藥物。
- 減肥注射劑（2021年）：研究2型糖尿病新藥時發現GLP-1類似物可顯著減重，催生Ozempic、Mounjaro等肥胖治療藥物。
原文鏈接：https://www.eurekalert.org/news-releases/1119254
本文通過A!翻譯。
