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dc.contributor.authorNie, F
dc.contributor.authorKunciw, DL
dc.contributor.authorWilcke, D
dc.contributor.authorStokes, JE
dc.contributor.authorGalloway, WRJD
dc.contributor.authorBartlett, S
dc.contributor.authorSore, HF
dc.contributor.authorSpring, DR
dc.date.accessioned2017-02-16T09:27:15Z
dc.date.available2017-02-16T09:27:15Z
dc.date.issued2016-09-05
dc.identifier.issn1433-7851
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/262549
dc.description.abstractSynthetic macrocycles are an attractive area in drug discovery. However, their use has been hindered by a lack of versatile platforms for the generation of structurally (and thus shape) diverse macrocycle libraries. Herein, we describe a new concept in library synthesis, termed multidimensional diversity-oriented synthesis, and its application towards macrocycles. This enabled the step-efficient generation of a library of 45 novel, structurally diverse, and highly-functionalized macrocycles based around a broad range of scaffolds and incorporating a wide variety of biologically relevant structural motifs. The synthesis strategy exploited the diverse reactivity of aza-ylides and imines, and featured eight different macrocyclization methods, two of which were novel. Computational analyses reveal a broad coverage of molecular shape space by the library and provides insight into how the various diversity-generating steps of the synthesis strategy impact on molecular shape.
dc.description.sponsorshipThe research leading to these results has received funding from the European Research Council under the European UnionÏs Seventh Framework Programme (FP7/2007–2013)/ ERC grant agreement no. [279337/DOS]. The authors also thank AstraZeneca, the EPSRC, the BBSRC, the MRC and the Wellcome Trust for funding. F.N. and D.L.K. thank the Gates Cambridge. F.N. also thanks Trinity College for a Krishnan-Ang Studentship. D.W. thanks the DFG for a postdoctoral fellowship (WI 4198/1-1). S.B. thanks the Herchel Smith Fund. The authors thank Dr John Davies for X-ray crystallography and Dr Andrew Bond for refinement (both from the University of Cambridge).
dc.languageeng
dc.language.isoen
dc.publisherWiley
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectdiversity-oriented synthesis
dc.subjectmacrocycles
dc.subjectmolecular diversity
dc.subjectsynthesis design
dc.subjectsynthetic methods
dc.titleA Multidimensional Diversity-Oriented Synthesis Strategy for Structurally Diverse and Complex Macrocycles
dc.typeArticle
prism.endingPage11143
prism.issueIdentifier37
prism.publicationDate2016
prism.publicationNameAngewandte Chemie International Edition
prism.startingPage11139
prism.volume55
dc.identifier.doi10.17863/CAM.7817
dcterms.dateAccepted2016-06-22
rioxxterms.versionofrecord10.1002/anie.201605460
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2016-09-05
dc.contributor.orcidBartlett, Sean [0000-0002-7044-4454]
dc.contributor.orcidSore, Hannah [0000-0002-6542-0394]
dc.contributor.orcidSpring, David [0000-0001-7355-2824]
dc.identifier.eissn1521-3773
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/J016012/1)
pubs.funder-project-idRoyal Society (WM150022)
pubs.funder-project-idEuropean Research Council (279337)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/K039520/1)
cam.issuedOnline2016-08-03
cam.orpheus.successThu Jan 30 10:20:25 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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