2-Nitroglycals: versatile intermediates for efficient and highly stereoselective base-catalyzed glycoside bond formations
This protocol describes the O-glycosyl trichloroacetimidate-based glycosylation of protected galactal 1 as acceptor under Sn(OTf)2 catalysis to give disaccharide 4. Nitration of the galactal moiety using nitric acid–acetic acid as nitrating agent followed by base-promoted acetic acid elimination affords the 2-nitro derivative 6 in a one-pot procedure. These types of intermediates can be used in the stereoselective synthesis of glycosides via Michael-type addition of alcohols as nucleophiles to 2-nitroglycals. Here, the base-catalyzed α-selective addition of N-Boc-protected Ser and Thr esters (7a, b) is described, which leads stereoselectively to adducts 8a, b. Transformation into the corresponding 2a-acetylamino derivates 9a, b provides versatile mucin core 1 building blocks (the total time for synthesizing 9a, b starting from 1 to 2 is typically 7 d with an overall yield of 18–25%). Also various other types of nucleophiles are amenable to this Michael-type addition 2-nitroglycals.