{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:27:35Z","timestamp":1786116455726,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The enantiomeric composition of products obtained from isomerization of n-humulone 1a to trans- and cis-n-isohumulones 2a and 3a, respectively, was determined by chiral HPLC analysis of the isolated trans and cis isomers. Enantiomers of humulone 1 were readily resolved on a Whelk-O1 chiral stationary phase (CSP), whereas the isomeric isohumulones 2 and 3 were separated on a carbohydrate-based IC-3 CSP. Magnesium-catalyzed isomerization of n-humulone under basic conditions gave mixtures of trans- and cis-n-isohumulones exhibiting an increasing preference for the cis isomer at lower temperatures. At either 10 \u00b0C in CH2Cl2\/H2O or reflux in methanol-water, the trans-(\u2212) (4S,5S)-2a isomer was obtained in greater than 95% ee, while diastereomeric cis-3a exhibited 88% ee of the (+)-(4S,5R) enantiomer. Precision continuous flow photochemical isomerization using 395 nm LEDs provided trans-(\u2212)-2a in greater than 95% ee in an isolated yield of 93%. However, photochemical isomerization with 365 nm LEDs gave a mixture of isomers consisting of 46% ee for the trans-(\u2212)-2a and greater than 95% ee for the cis-(\u2212)-(4R,5S)-3a enantiomer. The photochemically obtained (\u2212)-3a isomer has the opposite absolute configuration compared to thermal isomerization. An oxadi-\u03c0-methane rearrangement is proposed to account for the formation of isohumulone isomers under photochemical conditions.<\/jats:p>","DOI":"10.3390\/molecules31152731","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:46:38Z","timestamp":1786009598000},"page":"2731","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enantioselectivity of Isomerization of n-Humulone to trans- and cis-n-Isohumulones"],"prefix":"10.3390","volume":"31","author":[{"given":"Bruce C.","family":"Hamper","sequence":"first","affiliation":[{"name":"Department of Chemistry & Biochemistry, University of Missouri\u2014St. Louis, 43 Benton Ct., St. Louis, MO 63121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Giovine","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, University of Missouri\u2014St. Louis, 43 Benton Ct., St. Louis, MO 63121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajamoni","family":"Jagan","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, University of Missouri\u2014St. Louis, 43 Benton Ct., St. Louis, MO 63121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, University of Missouri\u2014St. Louis, 43 Benton Ct., St. Louis, MO 63121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Briggs, D.E., Boulton, C.A., Brookes, P.A., and Stevens, R. 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