title: Selective transformations of complex molecules are enabled by aptameric protective groups.
abstract: Emerging trends in drug discovery are prompting a renewed interest in natural products as a source of chemical diversity and lead structures. However, owing to the structural complexity of many natural compounds, the synthesis of derivatives is not easily realized. Here, we demonstrate a conceptually new approach using oligonucleotides as aptameric protective groups. These block several functionalities by non-covalent interactions in a complex molecule and enable the highly chemo- and regioselective derivatization (>99%) of natural antibiotics in a single synthetic step with excellent conversions of up to 83%. This technique reveals an important structure-activity relationship in neamine-based antibiotics and should help both to accelerate the discovery of new biologically active structures and to avoid potentially costly and cumbersome synthetic routes.
authors.affiliation: Zernike Institute for Advanced Materials, Department of Polymer Chemistry, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Bastian
authors.forename: Alessio
authors.initials: A
authors.lastname: Marcozzi
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
mesh_terms: D000215:Acylation; D000617:Aminoglycosides / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D008543:Melanins / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009355:Neomycin / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D052157:Aptamers, Nucleotide; D008543:Melanins; D009355:Neomycin