THEOBROMA: an aggregated open database of 1.13 million natural products with per-compound license auditing, three-tier classification, and stereochemistry-aware deduplication

Natural products remain one of the most productive sources of pharmacologically active compounds for drug discovery. Open aggregators attribute licenses at database granularity, and the consequences of that choice have become tangible as the field grows. A recent relicensing event in one constituent source (the September 2024 transition of the Natural Products Atlas to CC BY-NC 4.0) demonstrates how database-level licensing propagates across an aggregate and motivates the per-compound audit framework presented here. The same peer cohort separately leaves classification provenance and stereoisomer-family relations coarser than either layer warrants. THEOBROMA, accessible at https://theobroma.l3s.uni-hannover.de , integrates 1,132,805 natural products from 29 open sources under a per-compound license audit that resolves each compound’s license tier across all attesting sources under a most-restrictive-wins rule, identifying 900,103 compounds (79.5%) under open-use licenses and providing the per-source attestation chain and resolved tier through a dedicated audit endpoint and a query- time license filter. A three-tier classification labels all but 21 compounds by the provenance of the assignment (55.3% curated source labels, 18.2% NPClassifier tool assignments, 26.5% model-inferred). Deduplication at the full 27-character InChIKey retains 1,132,805 entries across 486,032 connectivity families, exposed via a dedicated /api/stereoisomers/<COMP id> endpoint and a radial-family display. Per-compound license provenance is the primary differentiator, while classification stratification and stereoisomer-family exposure add finer-grained access to two related axes, supporting license-compatible virtual screening and isomer-specific bioactivity analysis at corpus scale. As an evolving open resource, THEOBROMA pairs continuous pipeline maintenance with interactive geographic, taxonomic, and chemical-space exploration. Graphical Abstract THEOBROMA integrates 1,132,805 natural products from 29 open sources across three axes. A per-compound license audit resolves each compound to the most restrictive tier attested by any source, giving 891,860 permissive open, 225,536 non-commercial, 8,243 public domain and 7,166 unspecified, so that 900,103 compounds (79.5%) are open-licensed. A three-tier classification records the provenance of each label as source-supplied (55.3%), tool-assigned (18.2%), or model-inferred (26.5%), leaving 21 compounds unclassified. Deduplication at the full 27-character InChIKey retains the stereochemical and protonation variants that 14-character truncation would erase, illustrated by the (E,E)- and (Z,E)-curcumin pair shown.