{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T15:30:41Z","timestamp":1761492641742,"version":"build-2065373602"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistrySelect"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Malaria is a parasitic disease caused by the parasite\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    which results in hundreds of thousands of deaths per year. The need for new drugs for the treatment of this disease is imperative as new resistant strains of\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    emerge. Previously, our group reported two related series of pyrrolidine\u2010based antimalarial compounds. While both series were found to be orally efficacious in a mouse infection model, some analogues also showed modest affinities for the hERG ion channel. Herein, we describe the attempted synthesis of \u03b2\u2010fluoro substituted pyrrolidine analogues of both chemotypes. In this work, we observed position\u2010dependent chemical instability of fluorine on the pyrrolidine ring. \u03b2\u2010fluoro substituted pyrrolidine (\u00b1)\u2010\n                    <jats:bold>3<\/jats:bold>\n                    was tested in the\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    3D7 assay and showed a 40\u2010fold loss of anti\u2010\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    potency with little change in weak hERG affinity at 10\u00a0\u00b5M. In an effort to expand the utility of this work, pyrrolidine (\u00b1)\u2010\n                    <jats:bold>1<\/jats:bold>\n                    and fluoropyrrolidine (\u00b1)\u2010\n                    <jats:bold>3<\/jats:bold>\n                    were also tested against the related apicomplexan parasite\n                    <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                    which causes cryptosporidiosis. Both compounds showed modest potency (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a010\u00a0\u00b5M and 12\u00a0\u00b5M, respectively), implying this series could be further optimized for treatment for cryptosporidiosis.\n                  <\/jats:p>","DOI":"10.1002\/slct.202403837","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:43:48Z","timestamp":1741740228000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis of \u03b2\u2010fluoropyrrolidines Designed to Reduce hERG Affinity in a Class of Antiparasitic Compounds"],"prefix":"10.1002","volume":"10","author":[{"given":"Tanner J.","family":"Schubert","sequence":"first","affiliation":[{"name":"Department of Chemistry School of Science and Engineering Saint Louis University  Saint Louis MO 63103 US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guadalupe","family":"Calixto","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Science and Engineering Saint Louis University  Saint Louis MO 63103 US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katelyn B.","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Science and Engineering Saint Louis University  Saint Louis MO 63103 US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suvajit","family":"Koley","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Science and Engineering Saint Louis University  Saint Louis MO 63103 US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linglin","family":"Dai","sequence":"additional","affiliation":[{"name":"Guangzhou Institutes for Biomedicine and Health Chinese Academy of Sciences  Guangzhou Guangdong 510530 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangzhou Institutes for Biomedicine and Health Chinese Academy of Sciences  Guangzhou Guangdong 510530 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5484-619X","authenticated-orcid":false,"given":"Marvin J.","family":"Meyers","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Science and Engineering Saint Louis University  Saint Louis MO 63103 US"},{"name":"Institute for Drug and Biotherapeutic Innovation Saint Louis University  St. Louis MO 63103 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