{
  "abstract": "Expert chemists perform retrosynthetic analysis in a strategic manner, where each reaction in a route is employed with a specific purpose, combined with mechanistic reasoning represented as electron-pushing arrows to visualize how bonds are formed or broken via electron redistribution. Yet contemporary single-step retrosynthesis models exhibit neither of these properties: their learned reaction distribution is fixed to that of the training data, and reactions are predicted via de-novo generation of the precursors or molecular graph edits, omitting the electron redistribution that governs the chemical transformations. We introduce Verso MAELLE, the first electron-pushing-based single-step retrosynthetic model, representing disconnections as continuous-time Markov chains (CTMC) comprised of edits in the electron space, and is trainable using a discrete flow matching formulation. Being a generative model, Verso MAELLE is optionally steerable at inference time through the Feynman-Kac (FK) framework, using rewards that promote certain types of disconnections. We show that besides in-distribution learning, Verso MAELLE can be steered toward cyclization reactions which are scaffold-constructive but underrepresented in the training corpus, via a ring-breaking reward. As a proof of concept, we show how the electron-pushing reasoning, learned from patented data, combined with a domino incentivizing reward, could steer Verso MAELLE toward creative and strategic disconnections, demonstrated on the key domino sequence that was used to synthesize Punctaporonin U, a complex natural product of the sesquiterpene family.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": "2611.03696",
  "author_total": 3,
  "authors": [
    {
      "name": "Octavian Susanu"
    },
    {
      "name": "Nguyen Xuan-Vu"
    },
    {
      "name": "Philippe Schwaller"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ac8m7pzpx6zd0.bib",
  "cited_by": 0,
  "doi": "10.48550/arxiv.2611.03696",
  "fulltext_url": null,
  "id": "ac8m7pzpx6zd0",
  "issns": [],
  "landing_url": "https://arxiv.org/abs/2611.03696",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": "CC0-1.0",
  "native_subjects": [
    [
      "arxiv",
      "physics.chem-ph"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://arxiv.org/pdf/2611.03696",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ac8m7pzpx6zd0.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:21:25Z",
      "native_id": "2611.03696",
      "source": "arxiv",
      "url": "https://arxiv.org/abs/2611.03696"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "arxiv:physics.chem-ph",
      "subfield": "physical"
    }
  ],
  "title": "Steerable Single-step Retrosynthesis with Electron-pushing Discrete Flow Matching and Feynman-Kac Steering",
  "title_text": "Steerable Single-step Retrosynthesis with Electron-pushing Discrete Flow Matching and Feynman-Kac Steering",
  "type": "preprint",
  "updated_at": "2026-11-06T18:21:01Z",
  "url": "https://research.draconitic.com/paper/ac8m7pzpx6zd0",
  "venue": "arXiv",
  "versions": []
}