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 alpha-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.
Reddy
B Gopal
BG
Fachbereich Chemie, Universität Konstanz, Fach M 725, D-78457 Konstanz, Germany.
Schmidt
Richard R
RR
D004187:Disaccharides / Q000138:chemical synthesis; D004952:Esters / Q000737:chemistry; D005690:Galactose / Q000031:analogs & derivatives* / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D009077:Mucins / Q000737:chemistry*; D013237:Stereoisomerism
C526593:3,4,6-tri-O-benzyl-2-nitrogalactal; D004187:Disaccharides; D004952:Esters; D006027:Glycosides; D009077:Mucins; D005690:Galactose