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dc.contributor.authorCiardiello, JJen
dc.contributor.authorGalloway, Warrenen
dc.contributor.authorO'Connor, CJen
dc.contributor.authorSore, Hannahen
dc.contributor.authorStokes, JEen
dc.contributor.authorWu, Yen
dc.contributor.authorSpring, Daviden
dc.date.accessioned2015-10-22T15:37:19Z
dc.date.available2015-10-22T15:37:19Z
dc.date.issued2017-06-23en
dc.identifier.citationTetrahedron 2015. doi: 10.1016/j.tet.2015.10.061en
dc.identifier.issn0040-4020
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252390
dc.description.abstractNaturally-derived macrocyclic compounds are associated with a diverse range of biological activities, including antibacterial effects, and there are over 100 marketed macrocycle drugs derived from natural products. However, synthetic macrocycles are widely considered to be poorly explored in antibiotic development (indeed, within drug discovery in general). This has been attributed to challenges associated with the generation of such compounds. Whilst there are synthetic methods that can produce large collections of structurally similar macrocycles (i.e., compounds with varying appendages based around similar core macrocyclic ring architectures) there is a relative dearth of strategies for the efficient generation of more structurally diverse macrocycle collections in which there is greater variation in the nature of macrocyclic scaffolds present. Such macrocycle collections should contain compounds with a broad range of biological activities (including antibacterial activities) and the requisite robust synthetic methodology useful for analogue synthesis and lead optimization once an active compound has been identified in a biological screen. Herein, we describe a new and expedient diversity-oriented synthesis (DOS) strategy for the generation of a library of novel structurally diverse macrocyclic compounds with a high level of scaffold diversity. The strategy is concise, proceeds from readily-available starting materials, is modular in nature and features a variety of macrocyclisation techniques. In this proof-of-concept study, the synthesis of several previously unreported macrocyclic compounds was achieved. Each of these macrocycles was based around a distinct molecular scaffold and contained natural product-like structural features (e.g., three-dimensionality and multiple hydrogen bond donors and acceptors) as well as synthetic handles for potential further elaboration. The successful generation of these macrocycles demonstrates the feasibility of the new DOS strategy as a synthetic platform for library generation.
dc.language.isoenen
dc.publisherElsevier
dc.rightsCreative Commons Attribution 4.0
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleAn expedient strategy for the diversity-oriented synthesis of macrocyclic compounds with natural product-like characteristicsen
dc.typeArticle
prism.endingPage3578
prism.issueIdentifier25en
prism.publicationDate2017en
prism.publicationNameTetrahedronen
prism.startingPage3567
prism.volume72en
dc.rioxxterms.funderEPSRC
dc.rioxxterms.funderBBSRC
dc.rioxxterms.funderMRC
dc.rioxxterms.funderERC
dc.rioxxterms.funderWellcome Trust
dcterms.dateAccepted2015-10-21en
rioxxterms.versionofrecord10.1016/j.tet.2015.10.061en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-06-23en
dc.contributor.orcidSore, Hannah [0000-0002-6542-0394]
dc.contributor.orcidSpring, David [0000-0001-7355-2824]
dc.identifier.eissn1464-5416
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idRoyal Society (WM150022)
pubs.funder-project-idEuropean Research Council (279337)
pubs.funder-project-idEPSRC (EP/J016012/1)
cam.issuedOnline2015-10-23en


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Creative Commons Attribution 4.0
Except where otherwise noted, this item's licence is described as Creative Commons Attribution 4.0