title: Enhanced stereoselectivity of alpha-mannosylation under thermodynamic control using trichloroacetimidates.
abstract: O-Specific polysaccharides of Vibrio cholerae O1, serotypes Inaba and Ogawa, consist of alpha-(1-->2)-linked N-(3-deoxy-L-glycero-tetronyl)perosamine (4-amino-4,6-dideoxy-D-mannose). The blockwise synthesis of larger fragments of such O-PSs involves oligosaccharide glycosyl donors that contain a nonparticipating 2-O-glycosyl group at the position vicinal to the anomeric center where the new glycosidic linkage is formed. Such glycosyl donors may bear at C-4 either a latent acylamino (e.g., azido) or the 3-deoxy-L-glycero-tetronamido group. While monosaccharide glycosyl donors, even those bearing a nonparticipating group at O-2 (e.g., methyl), and the 4-N-(3-deoxy-L-glycero-tetronyl) side chain form alpha-linked oligosaccharides with excellent stereoselectivity, alpha-mannosylation with analogous oligosaccharide donors in this series is adversely affected by the presence of the side chain. Consequently, the unwanted beta-product is formed in a considerable amount. Conducting the reaction at elevated temperature under thermodynamic control substantially enhances formation of the alpha-linked oligosaccharide. This effect is much more pronounced when glycosyl trichloroacetimidates, rather than thioglycosides or glycosyl chlorides, are used as glycosyl donors.
authors.affiliation: NIDDK, LBC, National Institutes of Health, Bethesda, MD 20892-0815, USA.
authors.forename: Shu-jie
authors.initials: SJ
authors.lastname: Hou
authors.forename: Pavol
authors.initials: P
authors.lastname: Kovác
mesh_terms: D000081:Acetamides; D062845:Chloroacetates; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry*; D015394:Molecular Structure; D019081:O Antigens / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics; D014238:Trichloroacetic Acid / Q000737:chemistry; D041241:Vibrio cholerae O1 / Q000737:chemistry*
chemical_list: D000081:Acetamides; D062845:Chloroacetates; D019081:O Antigens; D014238:Trichloroacetic Acid; C009528:trichloroacetamide; D008358:Mannose
references.citation: Glycoconj J. 1997 Jun;14(4):433-8
references.pmid: 9249140
references.citation: Carbohydr Res. 1997 May 19;300(4):329-39
references.pmid: 9210300
references.citation: Carbohydr Res. 1998 Jan;306(1-2):163-70
references.pmid: 9691445
references.citation: Carbohydr Res. 1997 Jan 2;297(1):1-92
references.pmid: 9042704
references.citation: Org Biomol Chem. 2003 Mar 7;1(5):775-84
references.pmid: 12929359
references.citation: Carbohydr Res. 1988 Mar 15;174:239-51
references.pmid: 2454158
references.citation: J Infect Dis. 2002 Apr 1;185(7):950-62
references.pmid: 11920320
references.citation: Carbohydr Res. 1996 Jul 19;288:85-98
references.pmid: 8765728
references.citation: Angew Chem Int Ed Engl. 2005 Oct 7;44(39):6315-8
references.pmid: 16172990
references.citation: Carbohydr Res. 2008 Feb 4;343(2):196-210
references.pmid: 18048016
references.citation: Carbohydr Res. 1996 Oct 31;293(2):173-94
references.pmid: 8938375
references.citation: Biochem Biophys Res Commun. 1993 Jan 15;190(1):302-7
references.pmid: 8422256
references.citation: Biochim Biophys Acta. 1979 May 1;584(2):346-52
references.pmid: 86366
references.citation: Carbohydr Res. 1996 Feb 7;281(1):47-60
references.pmid: 8839176