{
  "abstract": "The difficulty in efficiently accessing to both enantiomers has long hampered the systematic evaluation of how chirality governs the bioactivity of natural products. We report a pathway-economical synthesis that addresses this challenge, unlocking enantiodivergent access to ten Aspidosperma alkaloids. The highlight of our strategy lies in an intermolecular enantioselective cycloaddition/retro-aza-Michael addition/DDQ-mediated skeletal reorganization cascade induced by Evans' auxiliary, which enables access to either enantiomeric series of the tetracyclic core from common starting materials simply by modulating the solvent. This synthesis enabled a comparative biological evaluation, uncovering starkly divergent antitumor mechanisms between enantiomers: (-)-vincadifformine acts through direct cytotoxicity, whereas its (+)-antipode is noncytotoxic but potently reverses T cell exhaustion via an immune-dependent mechanism. This work not only solves a longstanding supply problem of the two enantiomers of Aspidosperma alkaloids, but, by decoupling cytotoxicity from immunostimulation, identifies (+)-vincadifformine as a promising lead for cancer immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Structure-Based Drug Design and Discovery, (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, China.",
    "Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.",
    "Institute of Drug Research in Medicine Capital of China, Shenyang Pharmaceutical University, Benxi 117000, China.",
    "Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xiang Li"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Simeng Wang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xiang He"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Guoyu Li"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jiamo Wu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jinming Hu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lu Yang"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Lihui Wang",
      "orcid": "0000-0002-6538-0855"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Maosheng Cheng",
      "orcid": "0000-0001-9073-4806"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yongxiang Liu",
      "orcid": "0000-0003-0364-0137"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/74qh0gen7pmz5.bib",
  "cited_by": 0,
  "doi": "10.1021/jacsau.6c01163",
  "fulltext_url": "https://europepmc.org/articles/PMC13714851",
  "id": "74qh0gen7pmz5",
  "issns": [
    "2691-3704"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953574",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1605|Advanced Synthetic Organic Chemistry"
    ]
  ],
  "openalex": "W7214062761",
  "pdf_url": "https://europepmc.org/articles/PMC13714851?pdf=render",
  "pmcid": "PMC13714851",
  "pmid": "42953574",
  "published": "2026-09-23",
  "publisher": "American Chemical Society",
  "ris": "https://research.draconitic.com/paper/74qh0gen7pmz5.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953574",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953574"
    },
    {
      "first_seen": "2026-11-01T12:22:16Z",
      "native_id": "PMC13714851",
      "source": "pmc",
      "url": "https://doi.org/10.1021/jacsau.6c01163"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Advanced Synthetic Organic Chemistry",
      "subfield": "organic"
    }
  ],
  "title": "A Pathway-Economical Synthesis Enabling Systematic Evaluation: Enantiodivergent Access to Aspidosperma Alkaloids Unlocks Divergent Antitumor Mechanisms.",
  "title_text": "A Pathway-Economical Synthesis Enabling Systematic Evaluation: Enantiodivergent Access to Aspidosperma Alkaloids Unlocks Divergent Antitumor Mechanisms.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:16Z",
  "url": "https://research.draconitic.com/paper/74qh0gen7pmz5",
  "venue": "JACS Au",
  "versions": []
}