{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:16:51Z","timestamp":1788535011180,"version":"build-2803163510"},"reference-count":38,"publisher":"American Chemical Society (ACS)","issue":"35","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"Shanghai Magnolia Talent Plan Pujiang Project","award":["24PJD042"],"award-info":[{"award-number":["24PJD042"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chiral arylvinyl-substituted 3-hydroxy-5-oxo esters are valuable motifs in pharmaceuticals, yet their enantiocontrolled synthesis remains challenging. Herein, we report a biocatalytic system using ketoreductases (KREDs) for the highly C3-selective reduction of arylvinyl-substituted 3,5-dicarbonyl esters. Through semirational protein engineering, RasADH-E189D afforded the representative (S)-products in 89\u201399% conversion and 93\u201399% ee. Complementary (R)-products were obtained using KmCR2 and several other variants with up to 97% conversion and &amp;gt;99% ee, including a key intermediate for the synthesis of pitavastatin. Preparative-scale reactions (greater than 100 mg) further demonstrated the practicality of this platform. Protein\u2013ligand docking among the substrate, cofactor, and KREDs provided mechanistic insights for great stereoselectivity.<\/jats:p>","DOI":"10.1021\/acs.orglett.6c03023","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T23:55:16Z","timestamp":1787529316000},"page":"11013-11018","source":"Crossref","is-referenced-by-count":0,"title":["Enantiodivergent\nC3-Selective Reduction of Arylvinyl-Substituted\n3,5-Dicarbonyl Esters Enabled by Engineered Ketoreductases"],"prefix":"10.1021","volume":"28","author":[{"given":"Xiaoqiu","family":"Wu","sequence":"first","affiliation":[{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Yao","sequence":"additional","affiliation":[{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]},{"name":"Marine Biomedical Science and Technology Innovation Platform of Lingang Special Area , ,","place":["Shanghai, China, 201306"]},{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0431-5160","authenticated-orcid":true,"given":"Yamin","family":"Zhufu","sequence":"additional","affiliation":[{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]},{"name":"Marine Biomedical Science and Technology Innovation Platform of Lingang Special Area , ,","place":["Shanghai, China, 201306"]},{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"2026090409104076300_cit1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1039\/b417466f","article-title":"Polyketide Stereotetrads in Natural Products","volume":"34","author":"Koskinen","year":"2005","journal-title":"Chem. 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Rev."},{"key":"2026090409104076300_cit27","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1002\/tcr.202100062","article-title":"Application\nof Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive\nMolecules: An Update (2018\u20132020)","volume":"21","author":"Li","year":"2021","journal-title":"Chem.\nRec."},{"key":"2026090409104076300_cit28","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1080\/00397911.2015.1128546","article-title":"Asymmetric Synthesis of (\u2212)-Leiocarpin\nA via (\u2212)-(S)-Goniothalamin Employing Julia\u2013Kocienski\nOlefination","volume":"46","author":"Meruva","year":"2016","journal-title":"Synth. Commun."},{"key":"2026090409104076300_cit29","doi-asserted-by":"publisher","first-page":"4102","DOI":"10.1002\/ejoc.201500356","article-title":"A Practical\nSynthesis of Rosuvastatin and Other Statin Intermediates","volume":"2015","author":"Tartaggia","year":"2015","journal-title":"Eur. J. Org. Chem."},{"key":"2026090409104076300_cit30","doi-asserted-by":"publisher","first-page":"3162","DOI":"10.1002\/ejoc.201600268","article-title":"Chemoenzymatic Synthesis of \u03b4-Keto \u03b2-Hydroxy Esters as\nUseful Intermediates for Preparing Statins","volume":"2016","author":"Tartaggia","year":"2016","journal-title":"Eur. J. Org. Chem."},{"key":"2026090409104076300_cit31","doi-asserted-by":"publisher","first-page":"5752","DOI":"10.1021\/jo00020a008","article-title":"Enantioselective Synthesis\nof \u03b2-Hydroxy \u03b4-Lactones: A New Approach\nto the Synthetic Congeners of 3-Hydroxy-3-methylglutaryl Coenzyme\nA Reductase Inhibitors","volume":"56","author":"Reddy","year":"1991","journal-title":"J. Org. Chem."},{"key":"2026090409104076300_cit32","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1039\/D3GC04344D","article-title":"Engineered Ketoreductase-Catalyzed\nStereoselective Reduction of Ethyl\n2\u2032-Ketopantothenate and Its Analogues: Chemoenzymatic Synthesis\nof D-Pantothenic Acid","volume":"26","author":"Hu","year":"2024","journal-title":"Green\nChem."},{"key":"2026090409104076300_cit33","doi-asserted-by":"publisher","first-page":"3575","DOI":"10.1039\/C9OB00051H","article-title":"Ketoreductase-Catalyzed\nStereoselective Bioreduction of \u03b1-Nitro Ketones","volume":"17","author":"Wang","year":"2019","journal-title":"Org. Biomol. 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