Base‐catalyzed glycosylations provide the basis for a new and general entry to the synthesis of mucin‐type O‐glycans. The desired α‐linked 2‐acetamidoglycosyl amino acids B are accessible selectively starting from glycals of type A. Fmoc=9‐fluorenylmethoxycarbonyl.
Michael addition of serine and threonine derivatives 4a–4c to 3,4,6‐tri‐O‐benzyl‐2‐nitro‐D‐galactal (1) afforded the corresponding 2‐deoxy‐2‐nitro‐α‐D‐galactopyranosides 5a–5c in good yield and stereoselectivity. 2‐deoxy‐2‐nitroglycosides 5a and 5b were reduced to the 2‐acetamido compounds by platinized Raney nickel T4. Manipulation of the protecting groups afforded known N‐Fmoc‐O‐(2‐acetamido‐3,4,6‐tri‐O‐acetyl‐2‐deoxy‐α‐D‐galactopyranosyl)‐L‐serine (8a) and ‐threonine (8b), valuable building blocks for O‐glycopeptide synthesis.
A 3,4-O-unprotected galactal derivative having bulky 6-O-TIPS protection (compound 2) could be regioselectively 3-O-glycosylated with O-(galactopyranosyl) trichloroacetimidates; depending on the protecting group pattern stereoselectively alpha- and beta-linked disaccharides were obtained. With O-(2-azido-2-deoxyglucopyransyl) trichloroacetimidate as donor (compound 10A), glycosylation of 2 and of a 6-O-unprotected galactal derivative led in acetonitrile as solvent exclusively to a beta(1-3)- and a beta(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 alpha-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.
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