Case Study: Optimizing Retrosynthesis with SmartChemistry® AI

Example Case Study using ChemAI’s SmartChemistry®

SmartChemistry® successfully identified a cost-effective and scalable synthesis route for Oxaspiroketone (figure 1), a key intermediate in Alzheimer’s clinical candidates. This route has been experimentally validated.

Challenge: Finding an Efficient Route to Oxaspiroketone

A major challenge in synthetic chemistry is designing scalable, high-yield routes for complex molecules. Oxaspiroketone, an important intermediate for Alzheimer’s drug candidates, required an optimized synthesis pathway. Existing AI-driven retrosynthesis models and human-led approaches identified only a five-step synthesis with a low 17% yield – a result constrained by precedent-based reaction similarity.

Figure 1 : Oxaspiroketone Target

In benchmarking the best possible route identified by alternative AI methodologies was a 5 step synthesis as shown in figure 2 with an ultimate 17% yield.  This involved the direct formation of the spiro fragment with all known chemistry available by proximity with examples reported in the literature.

Figure 2 : Direct formation of a spiro fragment

Using its proprietary AI-driven retrosynthesis, SmartChemistry® identified a breakthrough alternative:

Figure 3 : Unique method to generate the spiro fragment identified in SmartChemistry

It is unlikely a chemist would intuitively identify this approach because the disconnection of bond c shown in figure 1 is at odds with the conventional wisdom in chemistry that the disconnection of two atoms both with partial negative charges likely.

✅ A 3-step synthesis route – Reducing complexity and improving efficiency.
✅ Over 40% yield – More than double the yield of traditional methods.
✅ Unconventional bond disconnection – A novel approach not predicted by conventional chemistry wisdom.

Results & Industry Impact

🔹 65% More Viable Routes Identified – Compared to the best alternative AI solutions.
🔹 Validated Experimentally – Demonstrating real-world success in synthesis efficiency.
🔹 Paradigm Shift in Retrosynthesis AI – SmartChemistry® moves beyond precedent-based approaches, unlocking hidden synthetic opportunities.

Conclusion
SmartChemistry® isn’t just an incremental improvement – it redefines what’s possible in retrosynthesis. By leveraging domain-specific AI, curated data, and advanced machine learning, it enables pharma and biotech companies to optimize synthetic routes faster, smarter, and more cost-effectively.

Ready to revolutionize your retrosynthesis? Contact us to learn how SmartChemistry® can accelerate your discoveries.