Synthesis of 2‐Amino‐2‐deoxy‐1,3‐dithioidoglycosides via Organocatalytic Relay Glycosylation of 3‐O‐Acetyl‐2‐nitrogalactals

Abstract

Comprehensive SummaryIdose‐type glycosides have numerous biological activities and have been widely used as anticoagulant drugs and anti‐infection drugs. Thioglycosides have enhanced stability for acid‐mediated or enzymatic hydrolysis, and have a wide range of applications in glycobiology and drug development. Herein, we describe an efficient method for site‐selective and stereoselective synthesis of potential bioactive 2‐amino‐2‐deoxy‐1,3‐dithioidoglycosides via organocatalysis sequential C3‐Ferrier rearrangement and Michael addition of 3‐O‐acetyl‐2‐nitrogalactals. Both stepwise and one‐pot protocols were carried out and work well. This unique thio‐glycosylation protocol highlighted the various advantages, including (i) mild reaction conditions; (ii) excellent site‐selectivity and stereoselectivity, good to excellent yields; (iii) broad substrate scopes; (iv) being atom‐economic and environmentally friendly; (v) the reactions can be scaled up.

Recent Advances of 2‐Nitroglycals as Powerful Glycosyl Donors

“…More recently, our group extended this novel organocatalysis one-pot relay glycosylation method to 2-nitrogalactal donor (Figure 19). [30] To our delight, potential bioactive 2amino-2-deoxy-1,3-dithioidoglycosides were furnished almost as single isomer in good yields. The reaction can be carried out in gram-scale, and the deprotection goes smoothly.…”