{
  "abstract": "The pharmacological performance of tenofovir alafenamide fumarate (TAF) hinges on a single stereogenic phosphorus atom, so its manufacture must deliver the P(S)-configured diastereomer in high stereochemical purity. Here we describe a preparation of TAF with a particular focus on diastereomer isolation. Resolution was first achieved at the chloro-PMPA monophenyl ester stage by crystallization-induced dynamic resolution (CIDR) in toluene, where selective deposition of the P(R)-isomer continuously withdraws it from the equilibrating mixture and shifts the system toward the desired configuration. This operation reproducibly furnished diastereomer P(S):P(R) ratio of 89:11. Residual P(R)-material was subsequently removed downstream by a biocatalytic step. Carboxypeptidase Y (CPY) hydrolyses the unwanted P(R)-diastereomer. Enzyme loading, organic solvent, buffer system, substrate concentration and temperature were systematically optimized, leaving the P(S)-product in greater than 99% diastereomeric purity and over 75% recovery. Steady-state kinetic measurements accounted for this selectivity: catalytic efficiency toward the P(R)-isomer exceeded that toward P(S) by 10-fold (kcat/KM = 304.3 versus 29.4 mM−1·min−1). The purified P(S)-isomer was carried forward as the key intermediate in the synthesis of TAF.",
  "abstract_shown": true,
  "affiliations": [
    "National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Suthathip Phetlum"
    },
    {
      "affs": [
        0
      ],
      "name": "Marie Hoarau",
      "orcid": "0000-0002-5758-3556"
    },
    {
      "affs": [
        0
      ],
      "name": "Thanat Tiyasakulchai",
      "orcid": "0009-0008-5677-8643"
    },
    {
      "affs": [
        0
      ],
      "name": "Nitipol Srimongkolpithak",
      "orcid": "0000-0003-2612-2770"
    },
    {
      "affs": [
        0
      ],
      "name": "Nongluck Jaito"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6y04c3m4v1nnt.bib",
  "cited_by": 0,
  "doi": "10.3390/molecules31213845",
  "fulltext_url": null,
  "id": "6y04c3m4v1nnt",
  "issns": [
    "1420-3049"
  ],
  "landing_url": "https://www.mdpi.com/1420-3049/31/21/3845",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Enzyme Catalysis and Immobilization"
    ]
  ],
  "openalex": "W7223654184",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-25",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/6y04c3m4v1nnt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:42Z",
      "native_id": "10.3390/molecules31213845",
      "source": "crossref",
      "url": "https://www.mdpi.com/1420-3049/31/21/3845"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Enzyme Catalysis and Immobilization",
      "subfield": "molecular-biology"
    }
  ],
  "title": "An Efficient Enzymatic Strategy for the Diastereoselective Isolation of Tenofovir Alafenamide",
  "title_text": "An Efficient Enzymatic Strategy for the Diastereoselective Isolation of Tenofovir Alafenamide",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:42Z",
  "url": "https://research.draconitic.com/paper/6y04c3m4v1nnt",
  "venue": "Molecules",
  "versions": []
}