Q&A WITH MERCK
FROM VISION TO REALITY: HARNESSING DIGITAL SOLUTIONS FOR BREAKTHROUGH INNOVATIONS IN CHEMICAL SYNTHESIS AND DRUG DISCOVERY
Q&A WITH MERCK
AQHow is SYNTHIA® reshaping the way chemists approach the earliest stages of drug discovery?
SYNTHIA® is fundamentally changing early drug discovery by empowering chemists to rapidly generate, visualize, and evaluate multiple synthetic routes for target molecules— even those never made before. By automating retrosynthetic analysis, we enable researchers to move from idea to actionable synthetic plans in minutes, not weeks. This accelerates hit-to-lead and lead optimization, reduces risk, and allows teams to focus their creativity on the most promising compounds.
QIn what ways do algorithms and machine learning give researchers an advantage over traditional retrosynthesis methods?
ASYNTHIA® combines expert-coded chemical rules with advanced algorithms and machine learning to scan vast chemical spaces and propose innovative, feasible pathways. Unlike traditional methods, which rely heavily on individual expertise and literature precedents, SYNTHIA® can uncover nonobvious disconnections, optimize for cost, step count, or green chemistry, and instantly access a catalog of over 12 million commercially available building blocks. This breadth and speed are simply not possible with manual planning.
QCould you share an example where SYNTHIA® directly influenced the success or speed of a synthesis project?
AAbsolutely. In a recent case, published in April this year, SYNTHIA®’s algorithms specified in planning shared synthetic pathway for multiple molecules, were connected to continuous flow chemistry. The study resulted in identifying and optimizing synthesis for multiple active pharmaceutical ingredients (APIs).
The results led to reduced resource use and improved operational conditions across multiple APIs. The integration of SYNTHIA® with continuous flow chemistry achieved a 95% isolated yield at optimized conditions, significantly enhancing productivity. The approach improved the overall environmental footprint, increasing the GreenMotion score by 25%, particularly in the 'Process' and 'Solvent' categories, indicating a more sustainable synthesis.
In summary, the combination of SYNTHIA® and flow chemistry allowed for greater flexibility and scalability in the production of multiple APIs, addressing challenges associated with traditional batch synthesis.
MERCK KGAA, DARMSTADT, GERMANY PROJECT DIRECTED BY: RUPERT KAY
FROM VISION TO REALITY: HARNESSING DIGITAL SOLUTIONS FOR BREAKTHROUGH INNOVATIONS IN CHEMICAL SYNTHESIS AND DRUG DISCOVERY
Q&A WITH MERCK Q&A
EWA GAJEWSKA
HEAD OF PRODUCT MANAGEMENT, SYNTHIA® RETROSYNTHESIS SOFTWARE
Dr. Ewa Gajewska is the Head of Product Management at Merck KGaA, Darmstadt, Germany, where she leads the development of SYNTHIA® Retrosynthesis Software – a groundbreaking software for computer-assisted synthetic planning. She graduated in biotechnology and chemistry from the Gdansk University of Technology and was a recipient of the Outstanding Achievements Award from Poland’s Minister of Science and Higher Education. In 2020 she received her PhD from the Institute of Organic Chemistry at the Polish Academy of Sciences. Her passion for tackling complex scientific challenges within commercial settings and the unique blend of her interdisciplinary skills drive the realization of innovative features of SYNTHIA Retrosynthesis Software.
QHow does the software encourage creativity in pathway design while ensuring the results are practical in the lab?
ASYNTHIA® acts as a creative partner, suggesting diverse, sometimes unconventional routes that chemists might not consider. At the same time, it grounds its suggestions in proven expert-coded reaction rules and published precedents, and allows users to filter by practicality—such as excluding hazardous reagents or requiring commercially available starting materials. This balance inspires new ideas while ensuring routes are realistic and executable.
QWhat impact can digital retrosynthesis tools have on cost efficiency and timelines in pharmaceutical R&D?
ADigital tools like SYNTHIA® can dramatically reduce both costs and timelines. By automating route scouting, minimizing failed experiments, and optimizing for cost-effective reagents, we’ve seen up to 90% reductions in manual planning time and significant savings in material and labor costs. This means faster progression from concept to candidate, and ultimately, to the clinic.
AQHow does SYNTHIA® support collaboration across research teams and disciplines?
SYNTHIA® is designed for collaboration. Users can share analyses, comment on pathways, and tag results for group projects. Our cloud-based platform ensures secure, realtime access for teams across locations and disciplines, making it easy for medicinal, process, and computation chemists to work together seamlessly.
QWhat are the biggest challenges you see in encouraging wider adoption of digital tools in chemical synthesis?
AThe main challenges are cultural and educational. Many chemists are used to traditional methods and may be skeptical of software predictions. We address this by demonstrating real-world successes, offering hands-on training, and emphasizing that SYNTHIA® is a tool to augment—not replace—human expertise. As more chemists experience the productivity gains, adoption is accelerating.
QAs drug targets grow more complex, how does SYNTHIA® help researchers navigate increasingly difficult synthesis routes?
ASYNTHIA® excels with complexity. Its algorithms can handle large, multifunctional molecules and propose routes that integrate both published and unpublished steps, predicted based on SYNTHIA®’s huge expert-coded rules database. For natural products and other challenging targets, SYNTHIA® has identified unique disconnections and strategies that have inspired successful syntheses, even when literature precedent is lacking.
AQWhat future developments or integrations do you see enhancing retrosynthesis software further?
We’re excited about deeper integration with AI-driven molecule design platforms, automated synthesis hardware, and green chemistry scoring tools. Our recent partnership with AIDDISON™ is a great example— combining generative AI for molecule design with SYNTHIA®’s synthesis planning creates an end-to-end digital workflow from virtual idea to real-world compound. We’re also expanding our API capabilities for seamless integration into enterprise R&D environments.
QDo you see digital intelligence as a supportive tool for chemists or something that could fundamentally transform how synthesis is carried out?
ADigital intelligence is both a supportive tool and a transformative force. It augments chemists’ intuition, accelerates routine tasks, and opens new creative possibilities. Ultimately, it’s not about replacing chemists, but empowering them to achieve more—faster, greener, and with greater confidence. The labs of the future will be defined by the synergy between human ingenuity and digital intelligence.
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