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Under green-chemistry conditions, the reactions occur in two key steps. The first one involves azeotropic activation of hydrogen peroxide for\n                    <jats:italic>N<\/jats:italic>\n                    -sulfonylpiperidone (\n                    <jats:bold>2a\u2013f<\/jats:bold>\n                    ), substituted cyclic and acyclic ketones (\n                    <jats:bold>2a<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sub>\n                    <jats:bold>\u2013a<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>4<\/jats:bold>\n                    <\/jats:sub>\n                    ) oxidation, whereas the second one was H\n                    <jats:sup>+<\/jats:sup>\n                    [BF\n                    <jats:sub>4<\/jats:sub>\n                    ]\u02c9 (50\u201355% solun; 25\u00a0mol%)-catalyzed cyclization of the highly reactive\n                    <jats:italic>gem<\/jats:italic>\n                    -dihydroperoxide (\n                    <jats:bold>3a\u2013f<\/jats:bold>\n                    and\n                    <jats:bold>3a<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sub>\n                    <jats:bold>\u2013a<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>4<\/jats:bold>\n                    <\/jats:sub>\n                    ) intermediates in an SN\n                    <jats:sub>1<\/jats:sub>\n                    -type manner with secondary keto compounds (\n                    <jats:bold>4a\u2013d<\/jats:bold>\n                    ). Both reactions furnished a diverse array of heterocyclic, cyclic, and open-chain 1,2,4,5-tetraoxane analogues (\n                    <jats:bold>5a\u2013l<\/jats:bold>\n                    and\n                    <jats:bold>6a\u2013k<\/jats:bold>\n                    ; 19\u201383%) in attainable yields. The outcomes of the control and competition experiment strongly indicate that the electronic effects of the EWGs group and the strong steric influence of the bulky\n                    <jats:italic>tri<\/jats:italic>\n                    -OMe-aryl group directly impacted reaction advancement. These effects were clearly observed in the reactivity of the substituted\n                    <jats:italic>N<\/jats:italic>\n                    -sulfonylpiperidones (\n                    <jats:bold>2a\u2013f<\/jats:bold>\n                    ) and\n                    <jats:italic>gem<\/jats:italic>\n                    -dihydroperoxides (\n                    <jats:bold>3a\u2013f<\/jats:bold>\n                    and\n                    <jats:bold>3a<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sub>\n                    <jats:bold>\u2013a<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>4<\/jats:bold>\n                    <\/jats:sub>\n                    ), and finally, also in the construction of the final products (\n                    <jats:bold>5a\u2013l<\/jats:bold>\n                    and\n                    <jats:bold>6a\u2013k<\/jats:bold>\n                    ). In addition, this metal-free approach is also suitable for the \u2018one pot\u2019 synthesis of structurally complex, highly substituted, pharmaceutically privileged\n                    <jats:italic>di<\/jats:italic>\n                    -\/\n                    <jats:italic>tri<\/jats:italic>\n                    -OMe-aryl-based cyclic and acyclic 1,2,4,5-tetraoxanes (\n                    <jats:bold>6a\u2013h<\/jats:bold>\n                    and\n                    <jats:bold>6k<\/jats:bold>\n                    ), offering significant potential for synthetic advancements in malaria and cancer chemotherapy. Furthermore, in preliminary biological evaluations, the in vitro antiplasmodial and cytotoxic potentials of novel\n                    <jats:italic>tri<\/jats:italic>\n                    -OMe-aryl-substituted\n                    <jats:italic>N<\/jats:italic>\n                    -sulfonylpiperidine-spiro-1,2,4,5-tetraoxanes (\n                    <jats:bold>5a\u2013l<\/jats:bold>\n                    ) were established against the chloroquine-resistant FcB1 strain of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    and human cancer cell lines, including HeLa and A2780 cells.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-48982-6","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:43:59Z","timestamp":1779709439000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficient and metal catalyst-free approach towards highly-substituted N-sulfonylpiperidine-\/mono-spiro-1,2,4,5-tetraoxanes for potential applications in chemotherapy"],"prefix":"10.1038","volume":"16","author":[{"given":"Mohit K.","family":"Tiwari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Kucinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Zgo\u0142a-Grze\u015bkowiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Grellier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Murias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"Marczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Popenda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Goslinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"issue":"10","key":"48982_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202400644","volume":"21","author":"MA Asmaey","year":"2024","unstructured":"Asmaey, M. 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