{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T10:27:06Z","timestamp":1792578426552,"version":"4.5.0"},"reference-count":96,"publisher":"American Chemical Society (ACS)","issue":"7","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101041783"],"award-info":[{"award-number":["101041783"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF21OC0067188"],"award-info":[{"award-number":["NNF21OC0067188"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Selective C\u2013H functionalization of small molecule leads is a powerful approach for efficient chemical space exploration and medicinal chemistry optimization. Here, we report a screening strategy for early- and late-stage chemoenzymatic oxidation of steroid-inspired compounds using a panel of P450BM3 variants. Late-stage oxidation of sterol transport protein inhibitors and their intermediates revealed enzyme- and substrate-dependent regioselectivity, which was rationalized by docking studies, and yielded hydroxylated analogues that provided rapid structure-activity relationship insights into the spirooxepinoindole as a privileged scaffold and its potential metabolic products. Early-stage functionalization of steroidal building blocks, including the Wieland-Miescher ketone and acetyl-cis-decalone, furnished hydroxylated derivatives with high diastereoselectivity. Notably, both enantiomers of both diastereoisomers of the C6-hydroxylated Wieland-Miescher ketone were obtained in preparative quantities, providing access to valuable early-stage building blocks for further derivatization. This work highlights the potential of chemoenzymatic approaches to deliver regio- and stereoselective oxidations of challenging steroid-like scaffolds, complementing classical synthetic methods and expanding opportunities in medicinal chemistry and natural product synthesis.<\/jats:p>","DOI":"10.1021\/jacsau.6c00535","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:54:36Z","timestamp":1782111276000},"page":"4014-4027","source":"Crossref","is-referenced-by-count":1,"title":["Early- and Late-Stage\nChemoenzymatic Functionalization\nof Steroid-Inspired Compounds"],"prefix":"10.1021","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7149-9246","authenticated-orcid":true,"given":"Frederik Simonsen","family":"Bro","sequence":"first","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-7379","authenticated-orcid":true,"given":"Thomas","family":"Whitmarsh-Everiss","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-9601","authenticated-orcid":true,"given":"Hogan P.","family":"Bryce-Rogers","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Depta","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Kubus","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Renata","sequence":"additional","affiliation":[{"name":"Rice University , , , ,","place":["Houston, Texas, United States, 77005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6692-3412","authenticated-orcid":true,"given":"Luca","family":"Laraia","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"issue":"9","key":"2026072709071776700_cit1","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1021\/acscentsci.8b00332","article-title":"Rationalizing\nSteroid Interactions with Lipid Membranes: Conformations, Partitioning,\nand Kinetics","volume":"4","author":"Atkovska","year":"2018","journal-title":"ACS Cent. 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Cell Factories"},{"issue":"15","key":"2026072709071776700_cit4","doi-asserted-by":"publisher","first-page":"8334","DOI":"10.1021\/acscatal.0c02077","article-title":"Oxidative\nDiversification of Steroids by Nature-Inspired Scanning Glycine Mutagenesis\nof P450BM3 (CYP102A1)","volume":"10","author":"Chen","year":"2020","journal-title":"ACS Catal."},{"issue":"5","key":"2026072709071776700_cit5","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.202301066","article-title":"Chemoenzymatic Synthesis of Steroidal\nProducts: Recent Advances","volume":"27","author":"Zheng","year":"2024","journal-title":"Eur. J. Org. 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