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Oxathiapiprolin (OXA), a potent OSBP\u2010targeting fungicide, represents the first commercially developed piperidine\u2010thiazole\u2010isooxazoline (PTI) product. Despite extensive structural modification focused on OXA, very few analogs with improved fungicidal activity have been identified to date.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In this study, a series of OXA derivatives were designed and synthesized by introducing a flexible acetal fragment into OXA. The compounds\n                      <jats:bold>B3<\/jats:bold>\n                      and\n                      <jats:bold>B5<\/jats:bold>\n                      respectively exhibited excellent 77.78% and 94.44% control efficiency against cucumber downy mildew (CDM) at 0.02\u2009mg\/L concentration. The field trials showed that compounds\n                      <jats:bold>B3<\/jats:bold>\n                      and\n                      <jats:bold>B5<\/jats:bold>\n                      took on higher control efficiency than OXA at the same concentration. The result of environmental toxicological risk assessment indicated that compounds\n                      <jats:bold>B3<\/jats:bold>\n                      and\n                      <jats:bold>B5<\/jats:bold>\n                      have lower toxicity to aquatic lives than OXA. Computational chemistry indicated that the binding mode of compound\n                      <jats:bold>B3<\/jats:bold>\n                      with\n                      <jats:italic>Phytophthora capsici<\/jats:italic>\n                      OSBP (\n                      <jats:italic>Pc<\/jats:italic>\n                      OSBP) is similar to that of OXA, and kept the main binding interaction with OSBPs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Our findings suggested that a strategy focused on increasing molecular flexibility could be advantageous for optimizing OSBP inhibitors. The chemical structure of compound\n                      <jats:bold>B3<\/jats:bold>\n                      may serve as a promising new starting point for the development of further OSBP inhibitors. \u00a9 2026 Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ps.70886","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:17:22Z","timestamp":1778213842000},"page":"8327-8337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and synthesis of oxathiapiprolin derivatives containing acetal fragments as potent fungicide candidates"],"prefix":"10.1002","volume":"82","author":[{"given":"Hong\u2010Hao","family":"Li","sequence":"first","affiliation":[{"name":"International Joint Research Center for Intelligent Biosensor Technology and Health Central China Normal University  Wuhan P. R. 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