Synthesis of Neokotalanol and Its Derivatives as Potent α-Glucosidase Inhibitors.
- 2025-10-04
- Organic letters 27(41)
- Yaojia Li
- Dan Liu
- Xuezheng Zhao
- Jiahui Zhou
- Yu Li
- Genzoh Tanabe
- Osamu Muraoka
- Wei Li
- Weijia Xie
- PubMed: 41045469
- DOI: 10.1021/acs.orglett.5c03549
A novel synthesis of neokotalanol, a sulfonium type α-glucosidase inhibitor derived from the genus Salacia, was developed. The strategy efficiently constructs the d-manno-heptitol side chain from 2-hydroxyglycal via cyclopropanation and ring-opening reaction. Stereoselective borohydride reduction of a 2,3-dicarbonyl intermediate installed two key chiral hydroxy groups. This Wittig-free method uses nontoxic reagents and achieves gram-scale synthesis of a key intermediate, enabling its first structural modification that highlights the critical role of C-6' hydroxyl for biological activity.