# Cycloadditions as a Sweet Route to ‘Double C-Glycosylation’

## 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.

## Key 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 cycloaddition chemistry to access new “double C-glycosylated” products and enables the creation of bridged polycyclic ethers from a common maltol-derived oxidopyrylium salt precursor.