Strategy-first synthesis planning for complex natural products

TL;DR - SynthEx is an LLM-based agentic framework that plans retrosynthetic routes to complex natural products that conventional, catalogue-driven design algorithms cannot handle, and expert chemists rated its key steps comparable to published human syntheses in blinded assessment.

• Frames the gap in existing tools: they are tuned to catalogued reaction benchmarks and report near-complete success there, but falter on densely functionalized, polycyclic natural products where inventive chemistry is least represented in the record.
• The agent proposes competing strategies, composes routine plus key steps into a cohesive route, then critiques and revises its own designs — a strategy-first rather than step-by-step search approach.
• Reported route characteristics: more convergent than existing tools' output, and covering a region of reaction space catalogue-based methods cannot reach.
• Releases SynthAtlas, an open interactive database of routes to 1,000+ natural products, targeting molecules lacking existing literature routes.