Glycal glycosylation and 2-nitroglycal concatenation, a powerful combination for mucin core structure 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.
Geiger
Jürgen
J
Fachbereich Chemie, Universität Konstanz, Fach M 725, D - 78457 Konstanz, Germany.
Reddy
B Gopal
BG
Winterfeld
Gottfried A
GA
Weber
R
R
Przybylski
M
M
Schmidt
R R
RR
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry; D002240:Carbohydrate Sequence; D005690:Galactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D008969:Molecular Sequence Data; D009077:Mucins / Q000138:chemical synthesis*
D015295:Antigens, Tumor-Associated, Carbohydrate; D006027:Glycosides; D009077:Mucins; C055491:sialosyl-Tn antigen; C002038:galactal; D005690:Galactose