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dc.contributor.authorCiardiello, JJ
dc.contributor.authorGalloway, WRJD
dc.contributor.authorO'Connor, CJ
dc.contributor.authorSore, HF
dc.contributor.authorStokes, JE
dc.contributor.authorWu, Y
dc.contributor.authorSpring, DR
dc.date.accessioned2015-10-22T15:37:19Z
dc.date.available2015-10-22T15:37:19Z
dc.date.issued2017-06-23
dc.identifier.citationTetrahedron 2015. doi: 10.1016/j.tet.2015.10.061
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.description.sponsorshipThe research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no [279337/DOS]. In addition, the group research was supported by grants from the Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Medical Research Council and Welcome Trust.
dc.language.isoen
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 characteristics
dc.typeArticle
prism.endingPage3578
prism.issueIdentifier25
prism.publicationDate2017
prism.publicationNameTetrahedron
prism.startingPage3567
prism.volume72
dc.rioxxterms.funderEPSRC
dc.rioxxterms.funderBBSRC
dc.rioxxterms.funderMRC
dc.rioxxterms.funderERC
dc.rioxxterms.funderWellcome Trust
dcterms.dateAccepted2015-10-21
rioxxterms.versionofrecord10.1016/j.tet.2015.10.061
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-06-23
dc.contributor.orcidSore, Hannah [0000-0002-6542-0394]
dc.contributor.orcidSpring, David [0000-0001-7355-2824]
dc.identifier.eissn1464-5416
rioxxterms.typeJournal Article/Review
pubs.funder-project-idRoyal Society (WM150022)
pubs.funder-project-idEuropean Research Council (279337)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/J016012/1)
cam.issuedOnline2015-10-23


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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