title: Modular Synthesis of Diverse Natural Product-Like Macrocycles: Discovery of Hits with Antimycobacterial Activity.
abstract: A modular synthetic approach was developed in which variation of the triplets of building blocks used enabled systematic variation of the macrocyclic scaffolds prepared. The approach was demonstrated in the synthesis of 17 diverse natural product-like macrocyclic scaffolds of varied (12-20-membered) ring size. The biological relevance of the chemical space explored was demonstrated through the discovery of a series of macrocycles with significant antimycobacterial activity.
authors.affiliation: School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK.|Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Dow
authors.affiliation: School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK.|Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marchetti
authors.affiliation: School of Biosiences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Abrahams
authors.affiliation: AstraZeneca, Charter Way, Macclesfield, SK10 2NA, UK.
authors.forename: Luis
authors.initials: L
authors.lastname: Vaz
authors.affiliation: School of Biosiences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.affiliation: School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK.|Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Warriner
authors.affiliation: School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK.|Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Adam
authors.identifier: http://orcid.org/0000-0003-3886-363X
authors.initials: A
authors.lastname: Nelson
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D055808:Drug Discovery; D006801:Humans; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009161:Mycobacterium / Q000187:drug effects*; D009164:Mycobacterium Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D047028:Macrocyclic Compounds
keywords: antimycobacterials; diversity-oriented synthesis; macrocycles