Synthonpedia: a sustainable and unbiased paradigm for the democratization of retrosynthetic knowledge

Retrosynthetic analysis is a fundamental pillar of organic synthesis, yet its execution is often constrained by human biases and the inherent limitations of current computational tools. While artificial intelligence (AI) has made significant strides in automating synthetic planning, many existing platforms operate as "black boxes" that inherit popularity biases from literature data. Here, we introduce Synthonpedia, a community-driven, open-access platform designed to redefine the retrosynthetic workflow through a human-machine cooperation model. Using “radical synthons” as data format organized in a database structure, Synthonpedia simplifies the algorithmic matching process and liberates chemical intuition from conventional reactivity trends. This streamlined logic results in a minimal computational footprint, enabling a complete retrosynthetitc analysis on consumer-grade hardware. We demonstrate the power of this approach through a proof-of-concept one-layer retrosynthesis of clavulanic acid, uncovering non intuitive disconnections that showcase the platform’s capacity for unbiased reaction space exploration. Synthonpedia stands as a sustainable, transparent infrastructure for the democratization of synthetic knowledge.