The C-disaccharide alpha-C(1 -> 3)-mannopyranoside of N-acetylgalactosamine is an inhibitor of glycohydrolases and of human alpha-1,3-fucosyltransferase VI. its epimer alpha-(1 -> 3)-mannopyranoside of N-acetyltalosamine is not

The radical C-glycosidation of (-)-(1S,4R,5R,6R)-6-endo-chloro-3-methylidene-5-exo-(phenylseleno)-7-oxa bicyclo[2.2.1]heptan-2-one ((-)-4) with 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl bromide gave (+)-(1S,3R,4R,5R,6R)-6-endo-chloro-5-exo-(phenylseleno)-3-endo-(1',3',4' ,5'-tetra-O-acetyl-2',6'-anhydro-7'-deoxy-D-glycero-D-manno-heptitol-7'- C-yl)-7-oxabicyclo[2.2.1]hept-2-one ((+)-5) that was converted into (+)-(1R,2S,5R,6R)-5-acetamido-3-chloro-2-anhydro-6-(1R,2S,5R,6R)-5-aceta mido-3-chloro-2-hydroxy-6-(1',3',4',5'-tetra-O-acetyl)-2',6'-anhydro-7'- deoxy-D- glycero-D-manno-heptitol-7'-C-yl)cyclohex-3-en-1-yl acetate ((+)-10) and into (+)-(1R,2S,5R,6S)-5-bromo-3-chloro-2-hydroxy-6-(1',3',4',5',-tetra-O-ace tyl-2',6'-anhydro-7'-deoxy-D-glycero-D-manno-heptitol-7'-C-yl)cyclohex-3 -en-1-yl acetate ((+)-19). Ozonolysis of (+)-10 and further transformations provided 2-acetamido-2,3-dideoxy-3-C-(2',6'-anhydro-7'-deoxy-D-glycero-D-manno- heptitol-7'-C-yl)-D-galactose (alpha-C(1-->3)-D-mannopyranoside of N-acetylgalactosamine (alpha-D-Manp-(1-->3)CH2-D-GalNAc): 1). Displacement of the bromide (+)-19 with NaN3 in DMF provided the corresponding azide ((-)-20) following a SN2 mechanism. Ozonolysis of (-)-20 and further transformations led to 2-acetamido-2,3-dideoxy-3-C-(2',6'-anhydro-7'-deoxy-D-glycerol-D-manno-h eptitol-7'-C-yl)-D-talose (alpha-C(1-->3)-D-mannopyranoside of N-acetyl D-talosamine (alpha-D-Manp-(1-->3)CH2-D-TalNAc): 2). The neutral C-disaccharide 1 inhibits several glycosidases (e.g., beta-galactosidase from jack bean with K-i = 7.5 mu M, alpha-L-fucosidase from human placenta with K-i = 28 mu M, beta-glucosidase from Caldocellum saccharolyticum with K-i = 18 mu M) and human alpha-1,3-fucosyltransferase VI (Fuc-TVI) with K-i = 120 mu M whereas it 2-epimer 2 does not. Double reciprocal analysis showed that the inhibition of Fuc-TVI by 1 displays a mixed pattern with respect to both the donor sugar GDP-fucose and the acceptor LacNAc with K-i of 123 and 128 mu M, respectively.

Published in:
Journal of Organic Chemistry, 65, 14, 4251-4260
Univ Lausanne, BCH, Chim Sect, CH-1015 Lausanne, Switzerland. Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland.

 Record created 2005-11-09, last modified 2018-12-03

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