{
  "abstract": "Retrosynthetic planning for discrete oligomers presents challenges that differ from those encountered for conventional small molecules because their synthesis often relies on repeated transformations applied at multiple related sites within a multistep route. In conventional template-based search, each application of a single-center reaction rule is represented as an independent action, causing repeated chemistry to consume additional search depth and potentially generating order-equivalent trajectories. Here, we showcase the adaptation of the SynPlanner retrosynthetic platform to oligomeric chemistry through the introduction of project-specific priority rules and a newly implemented Rule Multi-Application (RMA) mechanism. RMA enables repeated applications of the same single-center rule to be represented within a single search expansion, with the multiplicity determined dynamically from the molecular structure. Composite rules were additionally used to provide sequence-level guidance for selected ordered transformations. The approach was evaluated on two literature-derived targets: a linear oligoacetylacetone-derived oligomer and a macrocyclic calix[3]pyrrole. For the linear target, baseline planning generated 161 complete routes across 20 strategic-bond-pattern (SBP) clusters but did not reproduce the literature strategy. Combining priority-rule guidance, RMA, and sequence-level abstraction enabled exact recovery of the reported pathway. For the macrocyclic target, baseline planning failed to identify a complete route even after increasing the search budget to 10,000 iterations, whereas the RMA-enabled guided configuration generated 65 complete routes across three SBP clusters, including routes reproducing the strategic-bond pattern of the literature synthesis. These results demonstrate that adapting a retrosynthetic planner to oligomeric chemistry requires not only access to relevant reaction knowledge but also an appropriate representation of repeated transformations during multistep search.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Chemoinformatics, UMR 7140 CNRS, University of Strasbourg, 4, rue B. Pascal, Strasbourg, France, 67000",
    "Chemistry Solutions, Life Science Solutions, Elsevier, Nielsen House, John Smith Drive, Oxford, United Kingdom, OX4 2WB",
    "Institute for Chemical Reaction Design and Discovery (WPI-ICReDD, Hokkaido University, Kita 21 Nishi 10, Kita-ku, Sapporo, Japan, 001-0021"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Almaz Gilmullin"
    },
    {
      "affs": [
        0
      ],
      "name": "Tagir Akhmetshin"
    },
    {
      "affs": [
        0
      ],
      "name": "Olga Klimchuk"
    },
    {
      "affs": [
        0
      ],
      "name": "Dragos Horvath"
    },
    {
      "affs": [
        1
      ],
      "name": "Timur Madzhidov"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuki Ide"
    },
    {
      "affs": [
        2
      ],
      "name": "Ruben Staub"
    },
    {
      "affs": [
        2
      ],
      "name": "Yasuhide Inokuma"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Alexandre Varnek",
      "orcid": "0000-0003-1886-925X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/51h8hw8dv3kf7.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010108/v1",
  "fulltext_url": null,
  "id": "51h8hw8dv3kf7",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010108/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1702|AI-based Problem Solving and Planning"
    ]
  ],
  "openalex": "W7220908868",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010108/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/51h8hw8dv3kf7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010108",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010108/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "source:chemrxiv",
      "subfield": "general"
    }
  ],
  "title": "Adaptation of a retrosynthetic tool to project-specific chemistry: oligomer synthesis case study",
  "title_text": "Adaptation of a retrosynthetic tool to project-specific chemistry: oligomer synthesis case study",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/51h8hw8dv3kf7",
  "venue": "ChemRxiv",
  "versions": []
}