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. Selective modifications of structurally complex molecules bearing multiple reactive functional groups often require cumbersome multistep synthetic efforts. Here, aptameric protective groups based on short RNA sequences are described — they bind to neamine antibiotics, simultaneously protecting several functionalities and enabling regio- and chemoselective functionalizations.

Cite this article

Bastian, A., Marcozzi, A. & Herrmann, A. Selective transformations of complex molecules are enabled by aptameric protective groups. Nature Chem 4, 789–793 (2012). https://doi.org/10.1038/nchem.1402

View full text

>> Full Text:   Selective transformations of complex molecules are enabled by aptameric protective groups