An improved synthesis of TRβ-selective thyromimetic GC-1

An improved synthesis of TRβ-selective thyromimetic GC-1 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article An improved synthesis of TRβ-selective thyromimetic GC-1 Xiaohui Chu, Jinjun Wang, Yanzhong Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6615757/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract A new efficient synthesis of TR β-selective thyromimetic GC-1 is described. The present strategy employs benzyl substituent as the exclusive protecting group, avoiding side reactions and simplifying the purification process in the last step. This paper reports 62% overall yield in six steps for total synthesis of GC-1 in multi-gram scale. The initial synthetic route is adaptable to analogue design and suitable for the preparation of other natural methylenebisphenols. Physical sciences/Chemistry Physical sciences/Chemistry/Organic chemistry Physical sciences/Chemistry/Synthesis thyroid hormones GC-1 hydrogenolysis reaction methylenebisphenols total synthesis Full Text Additional Declarations No competing interests reported. Supplementary Files SupportingInformation.pdf Cite Share Download PDF Status: Published Journal Publication published 23 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 10 Jun, 2025 Reviews received at journal 10 Jun, 2025 Reviews received at journal 03 Jun, 2025 Reviewers agreed at journal 31 May, 2025 Reviewers agreed at journal 31 May, 2025 Reviewers invited by journal 30 May, 2025 Editor assigned by journal 30 May, 2025 Editor invited by journal 27 May, 2025 Submission checks completed at journal 21 May, 2025 First submitted to journal 21 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6615757","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":464612485,"identity":"b44c521f-639e-4966-931e-e3d74a013ca8","order_by":0,"name":"Xiaohui Chu","email":"","orcid":"","institution":"Yantai Institute of Technology","correspondingAuthor":false,"prefix":"","firstName":"Xiaohui","middleName":"","lastName":"Chu","suffix":""},{"id":464612486,"identity":"0c91ff2f-f5da-498d-a6af-03d385168584","order_by":1,"name":"Jinjun Wang","email":"","orcid":"","institution":"Yantai Institute of Technology","correspondingAuthor":false,"prefix":"","firstName":"Jinjun","middleName":"","lastName":"Wang","suffix":""},{"id":464612487,"identity":"6522af5f-dee1-4714-8a9a-afc78d451863","order_by":2,"name":"Yanzhong Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIie3RMUvDQBTA8QsHL8vDridC+hVOAhGJtl8lR6BdRAqCZLwSOL9CBcGvkNXtjoN2Cc6BLoqrYLo4VtOsNiGjw/3Hx/148I4Ql+sfNqKe1El2heDn5i0jtJ2yPnL6kC91Xc6CE1ynvBxCeLnJzaOyYcBuIjaIkEpIi0CFIkmUGRWPLwg1WyST2y7hrQ4EoSF6Vhk1P3+RkMZI0rsuQtmBMBTKk+vtTlmv0BidIdFCdhBoCWdCUU8tjLLTQo++ewmikWaV8BCAAmmIaLZAL2H+UupaJwE0N2D6dZ4WFsLLJ552kqn1P2qx/8Hx89eu1vfxdbHJ36vPbNJJjtR+DR/+3uVyuVx/+wUcdV+eYrqB+gAAAABJRU5ErkJggg==","orcid":"","institution":"Yantai Institute of Technology","correspondingAuthor":true,"prefix":"","firstName":"Yanzhong","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-05-08 02:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6615757/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6615757/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-12379-8","type":"published","date":"2025-07-23T15:57:32+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87756690,"identity":"3ae45604-33c8-481e-bdd8-b60247875ff5","added_by":"auto","created_at":"2025-07-28 16:07:45","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":448812,"visible":true,"origin":"","legend":"","description":"","filename":"AnimprovedsynthesisofTRselectivethyromimeticGC1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6615757/v1_covered_ca48a003-0a43-495d-8a7a-edf75bae6b53.pdf"},{"id":83789408,"identity":"489573a0-14ed-446d-bcdb-0b025d8d50b8","added_by":"auto","created_at":"2025-06-02 18:28:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":677492,"visible":true,"origin":"","legend":"","description":"","filename":"SupportingInformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6615757/v1/8280bbf3eac4f383b583e69c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"An improved synthesis of TRβ-selective thyromimetic GC-1","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"thyroid hormones, GC-1, hydrogenolysis reaction, methylenebisphenols, total synthesis","lastPublishedDoi":"10.21203/rs.3.rs-6615757/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6615757/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"A new efficient synthesis of TR β-selective thyromimetic GC-1 is described. 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