Single-Step Glycosylations with 13C-Labelled Sulfoxide Donors: A Low-Temperature NMR Cartography of the Distinguishing Mechanistic Intermediates |
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Authors: | Dr Andrés G Santana Dr Laura Montalvillo-Jiménez Laura Díaz-Casado Dr Enrique Mann Prof Jesús Jiménez-Barbero Dr Ana M Gómez Dr Juan Luis Asensio |
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Institution: | 1. Glycochemistry and Molecular Recognition group, Dpt. Bio-Organic Chemistry, Instituto de Química Orgánica General (IQOG-CSIC), Juan de la Cierva 3., 28006 Madrid, Spain;2. Center for Cooperative Research in Biosciences (CIC-bioGUNE), 48160 Derio, Spain;3. Oligosaccharide and Glycosystems group, Dpt. Bio-Organic Chemistry, Instituto de Química Orgánica General (IQOG-CSIC), Juan de la Cierva 3., 28006 Madrid, Spain |
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Abstract: | Glycosyl sulfoxides have gained recognition in the total synthesis of complex oligosaccharides and as model substrates for dissecting the mechanisms involved. Reactions of these donors are usually performed under pre-activation conditions, but an experimentally more convenient single-step protocol has also been reported, whereby activation is performed in the presence of the acceptor alcohol; yet, the nature and prevalence of the reaction intermediates formed in this more complex scenario have comparatively received minimal attention. Herein, a systematic NMR-based study employing both 13C-labelled and unlabelled glycosyl sulfoxide donors for the detection and monitoring of marginally populated intermediates is reported. The results conclusively show that glycosyl triflates play a key role in these glycosylations despite the presence of the acceptor alcohol. Importantly, the formation of covalent donor/acceptor sulfonium adducts was identified as the main competing reaction, and thus a non-productive consumption of the acceptor that could limit the reaction yield was revealed. |
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Keywords: | carbohydrates glycosylation isotopic labelling NMR spectroscopy reaction mechanisms |
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