{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:42:36Z","timestamp":1760236956779,"version":"build-2065373602"},"reference-count":20,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:00:00Z","timestamp":1580342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009894","name":"Politechnika L\u00f3dzka","doi-asserted-by":"publisher","award":["W-3D\/FMN\/24G\/2019"],"award-info":[{"award-number":["W-3D\/FMN\/24G\/2019"]}],"id":[{"id":"10.13039\/501100009894","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["503\/1-156-02\/503-11-001-19-00"],"award-info":[{"award-number":["503\/1-156-02\/503-11-001-19-00"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In our continuous search for new, relatively simple 2-alkylidene-1-oxoheterocycles as promising anticancer drug candidates, herein we report an efficient synthesis of 2,2,6-trisubstituted 5-methylidenetetrahydropyran-4-ones. These compounds were obtained in a four step reaction sequence, in which starting diethyl 2-oxopropylphosphonate was transformed into 2,2-disubstituted 5-diethoxyphosphoryldihydropyran-4-ones, followed by Michael addition of various Grignard reagents and Horner-Wadsworth-Emmons reaction of the obtained adducts with formaldehyde. Stereochemistry of the intermediate Michael adducts is also discussed. Final 5-methylidenetetrahydropyran-4-ones were tested for their possible antiproliferative effect against three cancer cell lines and 6-isopropyl-2,2-dimethyl-5-methylidenetetrahydropyran-4-one (11c), which showed very high cytotoxic activity against HL-60 human leukemia cells and was three times more active than known anticancer drug carboplatin, was selected for further biological evaluation, in order to disclose its mechanism of action. The obtained results indicated that 11c induced apoptosis in HL-60 cells and caused the arrest of the cell cycle in the G2\/M phase, which may suggest its cytotoxic and cytostatic activity.<\/jats:p>","DOI":"10.3390\/molecules25030611","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T05:55:46Z","timestamp":1580450146000},"page":"611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synthesis of 2,2,6-Trisubstituted 5-Methylidene-tetrahydropyran-4-ones with Anticancer Activity"],"prefix":"10.3390","volume":"25","author":[{"given":"Tomasz","family":"Bartosik","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry, Lodz University of Technology, \u017beromskiego 116, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"K\u0119dzia","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Lodz University of Technology, \u017beromskiego 116, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Drogosz-Stachowicz","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, Medical University of \u0141\u00f3d\u017a, Mazowiecka 6\/8, 92-215 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Janecka","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, Medical University of \u0141\u00f3d\u017a, Mazowiecka 6\/8, 92-215 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urszula","family":"Krajewska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Faculty of Pharmacy, Medical University of \u0141\u00f3d\u017a, Muszy\u0144skiego 1, 90-151, \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Mirowski","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Faculty of Pharmacy, Medical University of \u0141\u00f3d\u017a, Muszy\u0144skiego 1, 90-151, \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4898-1405","authenticated-orcid":false,"given":"Tomasz","family":"Janecki","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Lodz University of Technology, \u017beromskiego 116, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"K\u0119dzia, J., Bartosik, T., Drogosz, J., Janecka, A., Krajewska, U., and Janecki, T. 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