Cycloadditions as a Sweet Route to ‘Double C-Glycosylation’
Kevin P. P. Mahoney, Rosemary Lynch, Rhea T. Bown, Sunil V. Sharma, Piyasiri Chueakwon, G. Richard Stephenson, David B. Cordes, Alexandra M. Z. Slawin, Rebecca J. M. Goss
TL;DR
Scientists developed a new chemical method to create double C-glycosylated compounds, which are important in drugs like antibiotics and diabetes treatments.
Contribution
A novel biomimetic approach using cycloaddition chemistry to synthesize double C-glycosylated products is introduced.
Findings
A maltol-derived oxidopyrylium salt precursor was used to create bridged polycyclic ethers.
The method enables the synthesis of compounds with double C-glycosylation, similar to natural products.
This approach could help in the development of new pharmaceuticals with improved bioactivity.
Abstract
Pharmaceuticals, such as the antibiotic erythromycin, and sodium-dependent glucose transporter (SGLT1 & SGTL2) inhibitors such as Bexagliflozin (diabetes) and Sotagliflozin (heart disease), are often sugar-decorated (glycosylated). Glycosylation is a key component of the binding motif in SGLT inhibitors and, in natural products, glycosylation often confers improved bioactivity and bioavailability. Whilst a single C-glycoside link between a sugar moiety and its aglycone core is a common feature in natural products isolated to date, only a small number, including the antibiotics granaticin and sarubicin, are covalently bonded twice to a single sugar moiety. The way in which this “double C-glycosylation” is naturally mediated is not yet known, yet has been speculated on. Here, we report the exploration and development of a potentially biomimetic procedure that utilises intermolecular…
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Taxonomy
TopicsCarbohydrate Chemistry and Synthesis · Glycosylation and Glycoproteins Research · Microbial Natural Products and Biosynthesis