SynthEx: Expert Chemists in Blinded Review Judged an LLM Agent's Synthesis Steps Comparable to Published Human Routes

arXiv 2608.07454·medium signalXBlueskyLinkedInCopy link

Retrosynthesis tools built on catalogued reactions report near-complete success on benchmarks drawn from that same catalogue, yet falter on complex natural products whose densely functionalized polycyclic architectures demand exactly the inventive chemistry the record contains least. SynthEx, an LLM-based agentic framework, proposes competing strategies, assembles routine and key steps into a cohesive route, then critiques and revises its own design — producing more convergent chemistry spanning reaction space catalogue-based tools cannot reach. In blinded assessment expert chemists judged its key steps comparable to published human syntheses and engaged with them as genuine plans; routes to over 1,000 natural products are released as the open SynthAtlas database.