Glycal Glycosylation and 2-Nitroglycal Concatenation, a Powerful Combination for Mucin Core Structure Synthesis

摘要

A 3,4-Ounprotected galactal derivative having bulky 6-O-TIPS protection (compound 2) could be regioselectively 3-0-glycosylated with O(galactopyranosyl) trichloroacetimidates; depending on the protecting group pattern stereoselectively α- and β-linked disaccharides were obtained. With 0-(2-azido-2-deoxyglucopyransyl) trichloroacetimidate as donor (compound 10A), glycosylation of 2 and of a 6-0-unprotected galactal derivative led in acetonitrile as solvent exclusively to a β(1-3)- and a β(1-6)-linked disaccharide, respectively. Nitration of the galactal moieties of the saccharides followed by Michael-type addition of serine and threonine derivatives (7a,b) installed the α-galacto-configuration, thus readily furnishing O-glycosyl amino acid building blocks for the incorporation of core 1, core 2, core 3, core 6, and core 8 structures into glycopeptides. 2-Nitrogalactal and 2-nitroglucal derivatives could be also successfully employed in glycoside bond formation via Michael-type addition in a reiterative manner, affording the corresponding core 5, core 7, and core 6 building blocks. In this approach, highly stereoselective glycoside bond formations were based exclusively on Michael-type addition to the nitro-enol ether moiety of the 2-nitroglycals. Hence, 2-nitroglycals are versatile intermediates for base-catalyzed glycoside bond formation.