2025 年的一个秋日，药明康德研发化学服务部（RCS）收到一封客户的邮件：他们急需设计并合成有生物活性的目标分子，却卡在了关键中间体环节，如果用传统方法合成如同在 " 迷宫 " 中打转，难以推进。

基于此前与药明康德长期合作建立的深度了解与信任，客户抱着希望前来询问：" 听你们说过有电化学技术平台，能试试合成这个分子吗？"

项目团队分析发现，从这个中间体到最终的目标分子生成，还要约 19～20 步反应。根据每一步的收率推算，该中间体的产量至少需要几十克，才能撑起后续的反应需求。

几十克，对于普通分子的合成而言很容易；但在这类复杂分子的合成道路上，却如同一座高不可攀的大山。

接到这一需求后，项目团队快速响应。好消息是，" 山 " 虽高，却并不是 " 无路可走 "。在此之前，公司内部的电化学技术团队已经积累了类似分子的合成技术知识与经验，更有全套的设备。

但挑战也同样尖锐——原来的分子没有取代基，可客户需要的中间体多带了特殊的取代基，反应性也因此天差地别。

面对难题，电化学团队没有退缩。他们先按图索骥，用行业已知方法测试，结果不出所料，反应无法进行、未得到目标产物。

既然老路走不通，那就自己开辟一条新路。团队一头扎进实验室，在已有知识基础上自行探索，发现不同的反应参数稍有偏差，结果便大相径庭。于是，他们一点点调整电解质的当量和浓度等参数，在形形色色的电极中不断筛选。经历几天的试错与推翻后，终于，更佳的反应条件浮出水面。

团队科学家密切配合，仅一周时间，便完成了这个中间体分子的 " 闯关突围 " ——从几乎不反应，到小试条件筛选、中试产物成功合成、再到几十克规模放大产物的交付，以及后处理、分离和检测工作，一气呵成。

图片来源：123RF

这超乎预料的速度与产量，让客户收获了额外的惊喜。第二周，客户随即下达了第二批几十克规模的放大项目，后续更多批次的放大项目也随之而来。这一关键中间体满足要求后，客户需要的最终目标分子也顺利合成，并完成了初步测试。

此前，这家 " 老客户 " 已经见证了药明康德的流动化学、金属催化、光催化等技术平台的能力，但与电化学 " 打交道 " 还是头一回。这次，他们亲眼见证了这柄 " 新利器 " 的锋芒，信赖再添几分。

从 " 冷门技术 " 到应用 " 风口 "

在攻克上述难题的过程中，药明康德电化学团队所用的技术全称为 " 有机电化学合成技术 "，是电化学学科的应用领域之一。

这项技术其实起源很早，但在近几十年的发展却一度沉寂。早在 19 世纪上半叶，法拉第（Faraday，" 电学之父 "）和科尔贝（Kolbe）就点亮了有机电化学的星火；20 世纪，马库斯（Marcus）的 " 电子转移理论 " 进一步为其完善了底层原理。然而，受限于电极材料和设备进展缓慢，这一技术长期坐着 " 冷板凳 "，发展速度明显不及光催化和金属催化。

直到 2017 年前后，在可持续发展、" 绿色化学 " 理念与新能源浪潮的推动下，电极材料、催化剂与反应设备纷纷换代升级，这一技术终于在沉寂中抬头。到 2020 年，该领域的相关论文数量相比 2010 年已然翻倍。同年，巴兰（Baran）课题组发表了一篇重要论文，这相当于一份标准化的有机电化学合成 " 用户操作指南 "，点燃了学术界的热情。产业界也闻风而动，2022 年的一项调查显示，全球 17 家大型药企中已有 15 家在积极应用或探索该技术。

实际上，在风口来临之前，药明康德已有十余年电化学技术应用经验，但仅限于 Shono 氧化这种经典反应。2022 年，基于对行业趋势的洞察，药明康德开始加大对电化学技术平台的投入。

" 电化学不管是对传统化学，还是对光化学等新技术，都是很好的补充。提早建设相关能力，我们就能提早探索它的优势与潜力，当未来客户项目来临时，我们便能拥有更多可选择的工具、应对更加游刃有余。如果等客户有了更多需求再建，那就来不及了。" 药明康德 RCS 电化学平台负责人的这番话，道出了药明康德对各类创新技术应用的远见和担当。

冷门利器初显 " 锋芒 "，已开发出几十余种反应类型

2022 年，药明康德 RCS 团队基于过去积累的经验，很快完成了实验设备和流程搭建，引入国际通用的电化学反应器，并建立了自主筛选反应参数的能力，从而更好地为客户提供条件筛选和放大支持服务。

在这个过程中，团队开展了大量研发尝试，不仅复现了文献报道的反应，还在未知领域自主探索，丰富电化学实操经验，以及与其他技术平台 " 打配合 " 的经验。当年之内，团队就凭借这一新技术完成了客户分子项目的交付。

到了 2025 年，也就是三年后，电化学反应数相比初期已呈爆发式增长。团队渐渐发现，这柄 " 新利器 " 能 " 切开 " 一些其他化学技术无可奈何的 " 死结 "：面对当下热门的靶向蛋白降解（TPD）分子合成，在卤卤偶联反应中使出电化学这招，成功率很高，几十克规模的合成不再是难题；对于带着大位阻的 BCP 环 NHP 酯与芳香卤代物的棘手反应，平台一年能护航几十个此类项目的交付；至于那些位阻型大环张力 NHP 酯偶联反应，电化学平台更有 " 化险为夷 " 的潜力，一年能 " 挽救 " 几十个采用光催化折戟的项目分子。

有业内人士称电化学是 " 黑科技 "，因为它在完成高难度反应的同时，过程和用具却往往十分朴素。比如在一个客户项目中，药明康德团队用价廉易得的双羧酸当原料，用成本相对低廉的 RVC 电极换下传统的贵金属铂电极，通过电化学技术脱羧偶联构建 C ( sp ³ ) -C ( sp ³ ) 键，高效合成了一种非天然 β - 氨基酸，将原本需 7 步的合成路线，" 抄近道 " 缩减至 1 步，收率更从 21% 跃升至 74%，实现了快速的毫克级制备。

随着成功案例的积累，越来越多以电化学为核心的赋能合作项目纷至沓来。如今，药明康德电化学平台每年能稳稳交付数百个分子。药明康德在多个基地均有电化学实验室和人员，已开发出几十余种电化学反应类型，单个反应可操作规模从百毫克级别到 200 克规模以上都能覆盖。

以 " 合成工具箱 "，更好地赋能创新

在药明康德的 CRDMO 赋能体系中，电化学与流动化学、金属催化、光催化等技术一起，共同构成了一个功能多样、全面的 " 合成工具箱 "。

以电化学与光化学为例：它们均是通过激发电子流动来实现分子的氧化还原与 " 移花接木 "，但各有专长、互为补充。光化学发展更为成熟，可催化反应类型更多；电化学则在某些特定的反应中优势独特：它操作简便，实验人员无需准备苛刻的无水无氧环境；它条件温和，能省去繁琐的基团保护步骤，缩短流程，从而提高收率；且反应后杂质少，目标产物的提纯更容易。

在热门的 C ( sp ² ) -C ( sp ³ ) 和 C ( sp ³ ) -C ( sp ³ ) 键的构建中，光化学是常用 " 主力 "，电化学则是有力的 " 补位 "，两者协同拓宽了合成的可能性。比如有一些分子，采取常用的光催化方式收率非常低，经电化学尝试后，收率显著提升，已经足以成功交付用于下一步生物测试。尤其是能为分子带来高 sp ³ 杂化特征的 C ( sp ³ ) -C ( sp ³ ) 键，近年研究发现其与药物后期研究的成功率息息相关，因此它的高效构建也成为行业致力追求的目标，而近年兴起的电化学催化脱羧偶联（rAP-Kolbe/dDCC）技术，正是构建这类分子结构的创新方法之一，能 " 锻造 " 出许多在传统反应中难以获得的高价值模块结构。

对于大位阻分子，电化学也可以帮光化学破局，让 " 光照不到的反应死角 " 无处遁形，从而破解大位阻 C ( sp ² ) -C ( sp ³ ) 卤卤偶联、NHP 酯偶联，乃至大位阻烷基醚的合成困局。

此外，电化学还能在这些方面 " 大显身手 "：在 C-N/C-O 键的构建上，电化学是对金属催化的补充；面对加压、危险试剂、气体等特殊反应，电化学更能以温和的方式化解风险。

据 RCS 电化学平台负责人介绍，面对合成路上的 " 拦路虎 "，团队往往会优先拿出成熟的技术，如果遇到阻碍，再果断切换电化学等可能有希望的技术。而对于已有经验的电化学优势反应，也会同时尝试多种技术，最终为客户提供更丰富的放大选择。

这种一体化 " 工具箱 " 式的协作，让越来越多复杂分子的合成成为可能，并顺利迈入后续阶段，推动客户项目稳步向前。尤其对于需要把握关键时间节点、试错空间较低的小型生物科技公司这样的客户而言，这种全面、稳定的能力，可以 " 挽救 " 更多传统方法望而却步的分子，更好地为客户的前沿创新的小分子或复杂分子项目保驾护航。

药明康德电化学平台的发展历程，是公司全面化学能力的生动侧写。正是这些深耕厚植、由专而全的技术工具，铺就了公司的一体化 CRDMO 赋能平台这片繁茂森林。

如今，药物分子量越来越大，合成难度越来越高，新型分子由于结构的复杂性，其分子量、合成难度以及合成步骤更是显著增长。但对能力全面的一体化 CRDMO 平台而言，这意味着更多机遇。在创新的浪潮中，药明康德深知，提早布局新能力、精益求精地打磨每一项技术能力，方能打造出更全面的 " 工具箱 " 式的一体化平台，更好地赋能全球创新。

未来，药明康德将继续跟随科学发展、跟随客户需求，跟随分子进程，持续夯实技术平台能力和规模，助力全球创新者突破新药研发瓶颈，加速客户的更多新疗法从实验室脱颖而出、来到患者身边。

了解药明康德研发化学服务部如何赋能药物研发，请长按扫描上方二维码，与药明康德研发化学服务部联系

From "No Reaction" to "Better-Than-Expected Production": How WuXi AppTec Uses Electrochemistry to Solve Synthetic Bottleneck?

On an autumn day of 2025, WuXi AppTec ’ s Research Chemistry Services ( RCS ) received an email from a customer: they needed to design and synthesize a bioactive target molecule but were stuck at a key intermediate step, and using conventional routes was hard to move forward.

Based on years of collaboration and trust, they asked the RCS team, "We heard you have an electrochemistry platform. Could you try to synthesize this molecule?"

The project team traced the synthesis from the intermediate to the target molecule and counted roughly 19 – 20 additional steps. Based on the expected yields for each step, the intermediate would require at least several tens of grams to sustain downstream work. For many simple syntheses, producing tens of grams is trivial, but for this class of complex molecules, it presents a high level of difficulty.

The team responded quickly. WuXi AppTec ’ s in-house electrochemistry team had previously accumulated relevant knowledge, experience, and a complete set of equipment. The challenge was significant: the intermediate previously synthesized in-house bore no substituents, whereas the customer ’ s target intermediate was expected to carry a specific substituent that notably altered reactivity.

The electrochemistry team first followed protocols guided by existing knowledge, but as expected, the reactions failed to produce the desired product. Rather than retreat, they decided to open a new path. Building on prior knowledge, they launched an intensive experimental campaign and found that small deviations in parameters led to much different outcomes. They methodically adjusted parameters including electrolyte equivalents and concentrations, and screened a variety of electrodes. After several days of iterative trial and error, optimized conditions emerged.

Working in close coordination,the electrochemistry team achieved rapid progression within one week: they progressed from virtually no reaction to lab-scale condition screening, succeeded in pilot-scale synthesis, and scaled up to deliver tens of grams of production— followed by downstream work on purification, separation, and analysis — just in one continuous effort. The unexpectedly rapid timeline and production delighted the customer. The following week, the customer placed a second tens-of-grams scale requirement, and further scale-up batches followed. With the key intermediate secured, the final target molecule was successfully synthesized and passed preliminary testing.

Image source: 123RF

Previously, the customer had seen WuXi AppTec ’ s capabilities in multiple synthetic technologies including flow chemistry, metal catalysis, and photochemistry, but this was their first direct collaboration on electrochemistry. During this project they witnessed the new platform ’ s effectiveness and gained confidence in the company ’ s capabilities.

Long Overlooked, a Niche Tool Finds Its Moment

In the process of tackling the above challenge, organic electrochemical synthesis is the applied branch of electrochemistry used by the team.

Although the field traces back to early pioneers — Faraday and Kolbe in the 19th century — and later theoretical advances such as Marcus ’ s electron-transfer theory, progress was limited by electrode materials and equipment for many decades. As a result, electrochemistry lagged behind photocatalysis and metal catalysis.

Around 2017, driven by sustainability and green-chemistry goals and improvements in electrode materials, catalysts, and reactors, the field began to revive. By 2020, the number of publications in synthetic electrochemistry had doubled compared with 2010. In the same year, Phil S. Baran ’ s group published an important paper, which served as a "user guide" for organic electrochemical synthesis and fueled the academic community ’ s enthusiasm for synthetic electrochemistry. Industry responded as well: a 2022 survey found that 15 of 17 large pharmaceutical companies were actively applying or exploring electrochemical methods.

In fact, before this niche tool found its moment, WuXi AppTec had applied electrochemistry in limited contexts — classical Shono oxidation — for over a decade. Based on insights into industry trends, the company increased investment in the electrochemistry platform in 2022.

"Whether for traditional chemistry or for newer methods such as photochemistry, electrochemistry serves as a strong complement. By building related capabilities early, we can begin to explore its advantages and potential in advance; when customer demands arise, we will be better prepared, since we have more tools to choose from. If we wait until customers demand it before we start building, it will place ourselves at a reactive position." said the head of the electrochemistry platform, whose remarks reveal WuXi AppTec ’ s strategic vision and sense of responsibility in applying various innovative technologies.

The Niche Tool Began to Show Its Edge: Dozens of Reaction Types Have Been Developed

In 2022, the electrochemistry team quickly established equipment, workflows, including adoption of internationally used electrochemical reactors, and developed an in-house capability for parameter screening, thereby enabling partners in condition screening and scale ‑ up. That year the team carried out extensive research efforts, reproduced literature reactions and explored new transformations, expanded their practical operating experience in electrochemistry and cross-platform collaboration skills. Within that year, the team had delivered multiple client projects by leveraging this new technology.

By 2025 — three years later — the number of electrochemical reactions the team handled had grown significantly. The platform exhibited a distinct advantage in complex synthesis challenges that other techniques struggled with. For example, in targeted protein degradation ( TPD ) molecule synthesis, applying electrochemistry to reductive homocoupling of alkyl and aryl halides produced high success rates and made tens-of-grams syntheses routine. The platform supported dozens of projects annually for tricky reactions between highly sterically hindered BCP-derived NHP esters and aryl halides, and it showed particular promise for coupling reactions of sterically hindered, strained-ring NHP esters, where photocatalysis methods sometimes fail. Each year, it can rescue dozens of project molecules that stalled under photochemistry approaches.

Electrochemistry is noted by industry observers as a highly effective yet easily deployable approach, capable of driving challenging reactions with simple apparatus. Take one customer project, for example,the team used inexpensive and readily available dicarboxylic acids and a relatively lower-cost RVC ( reticulated vitreous carbon ) electrode instead of costly platinum.Through electrochemical decarboxylative coupling, they built a C ( sp3 ) – C ( sp3 ) bond to synthesize a non-natural β -amino acid efficiently,streamlining the original 7-step synthesis route into just one step, and raising yield from 21% to 74% for rapid milligram-scale preparation.

Image source：123RF

As successful cases accumulated, a growing number of electrochemistry-driven collaborative initiatives are pouring in. Today, the platform reliably delivers hundreds of molecules per year. WuXi AppTec maintains electrochemistry labs and scientists across multiple sites and has developed dozens of electrochemical reaction types. Individual reactions are operable from sub-100 mg scales up to over 200 g.

Leveraging the "Synthesis Toolbox" to Better Enable Innovation

The electrochemistry platform forms part of WuXi AppTec ’ s CRDMO "synthesis toolbox", alongside flow chemistry, metal catalysis, and photochemistry. These technologies are complementary, and the "toolbox" approach broadens synthetic options for partners.

For example, electrochemistry and photochemistry both drive electron flow to accomplish oxidation – reduction transformations. The two are highly complementary, while each excels in different niches. Photochemistry is a well-developed area, and offers a wider range of reaction types; electrochemistry, however, has advantages in specific reactions: it is operationally simple ( often avoiding rigorous anhydrous or oxygen-free conditions ) ; uses mild conditions that can eliminate group-protecting steps and shorten sequences, thus significantly improving yields; and typically produces fewer impurities, easing purification.

For constructing C ( sp ² ) – C ( sp ³ ) and C ( sp ³ ) – C ( sp ³ ) bonds, photochemistry is often the primary tool while electrochemistry provides powerful support. Some molecules that give low yields with photocatalysis methods show significant yield improvements under electrochemical approaches, enabling successful delivery for downstream biological testing. For example, high-sp ³ fragments are increasingly linked to clinical success, so efficient methods for building C ( sp ³ ) – C ( sp ³ ) bonds are highly demanded; recently developed electrochemical decarboxylative coupling ( rAP-Kolbe/dDCC ) is one such innovation that accesses valuable modules difficult to obtain conventionally.

Electrochemistry can also supplement photochemistry for sterically hindered systems, resolving "dark" reaction pockets where photochemistry driven methods are ineffective. It aids in challenging cross-electrophile coupling for sterically hindered C ( sp ² ) – C ( sp ³ ) bond formation, NHP ester couplings, and synthesis of sterically hindered alkyl ethers. Additionally, electrochemical methods can complement metal catalysis in constructing C – N and C – O bonds, and they offer milder solutions for reactions that would otherwise require pressure, hazardous reagents, or gases.

The electrochemistry platform leader notes that when synthesis encounters a barrier, the team first applies mature methods and then, if needed, decisively switches to electrochemistry or runs multiple approaches in parallel to give customers more scalable options. This "toolbox" integration makes many complex syntheses feasible and helps projects progress to later stages, especially for small biotech customers who must meet tight timelines with limited opportunity for trial and error. For such customers, a comprehensive, reliable capability enables them to rescue molecules that conventional synthesis leaves behind, thus de-risking and better advancing early-stage innovation.

WuXi AppTec ’ s electrochemistry platform development mirrors the company ’ s broader chemical capability: methodical, cumulative work that builds an integrated CRDMO enabling platform.

Nowadays, as new modalities grow larger and more complex, synthesis becomes harder and routes lengthen; for a broadly capable integrated end-to-end CRDMO platform, these trends represent an opportunity. WuXi AppTec believes that early investment and continuous refinement of technical capabilities are essential to building a comprehensive integrated "technology toolbox" that enables global innovators.

In the future, WuXi AppTec will continue to align with scientific progress, respond to evolving customer needs, keep pace with advances in molecular complexity, and continuously scale capabilities and infrastructure, to enable global innovators in overcoming new drug development bottlenecks, and support their efforts to bring innovative treatments from the lab to patients.

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