Rolf Lebuhn

Synthese einer verzweigten pentasaccharid-sequenz der “bisected” struktur von N-glycoproteinen

For the synthesis of the threefold-branched pentasaccharide, O-alpha-D-mannopyranosyl-(1----3)-O-[(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----4)]-O-[alpha-D-mannopyranosyl-(1----6)]-O-beta-D- mannopyranosyl-(1----4)-2-acetamido-2-deoxy-D-glucopyranose (20), which is a part of the structure of the N-glycoproteins, the disaccharide 4-O-(4-O-acetyl-3,6-di-O-allyl-2-O-benzyl-beta-D-mannopyranosyl) -1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranose was synthesized as a key compound by use of the silver silicate-catalyst procedure. After elimination of the 4-O-acetyl group, a 2-acetamido-2-deoxy-beta-D-glucopyranosyl group was attached according to the phthalimido method. Further elimination of the allyl groups allowed the linkage of two alpha-D-mannopyranosyl groups in the presence of mercury salt. A deblocking sequence consisting of four steps gave 20.

Synthese der invarianten pentasaccharid-core-region der kohlenhydrat-ketten der N-glycoproteine

Abstract 6- O -Acetyl-3- O -benzyl-2-deoxy-4- O -(3,6-di- O -allyl-2,4-di- O -benzyl-β- d -mannopyranosyl)-2-phthalimido-β- d -glucopyran osyl chloride ( 9 ) was synthesized in a five-step reaction from 1,6-anhydro-2-azido-3- O -benzyl-2-deoxy-4- O -(6- O -acetyl-3- O -allyl-2,4-di- O -benzyl-β- d -mannopyranosyl)-β- d -glucopyr anose. The block synthesis of 9 with benzyl 2-acetamido-3,6-di- O -benzyl-2-deoxy-α- d -glucopyranoside forming a β- d -glycosidic linkage gave a trisaccharide that was deblocked to yield O -β- d -mannopyranosyl-(1→4)- O -(2-acetamido-2-deoxy-β- d -glucopyranosyl)-(1→4)-2-acetamido-2-deoxy- d -glucopyranose. Condensation of benzyl O -(2,4-di- O -benzyl-β- d -mannopyranosyl)-(1→4)- O -(6- O -acetyl-3- O -benzyl-2-deoxy-2-phthalimido-β- d -glucopyranosyl)-(1 →4)-2-acetamido-3,6-di- O -benzyl-2-deoxy-α- d -glucopyranoside with an excess of 2- O -acetyl-3,4,6-tri- O -benzyl-α- d -mannopyranosyl chloride gave a pentasaccharide that was deprotected to afford O -α- d -mannopyranosyl-(1→3)-[ O -α- d -mannopyranosyl-(1→6)]- O -β- d -mannopyranosyl-(1→4)- O -(2-acetamido-2-deoxy-β- d -glucopyranosyl)-(1→4)-2-acetamido-2-deoxy- d -glucopyranose which represents the core region of the carbohydrate chains of the N -glycoproteins.

Synthese von pentasaccharid- und octasaccharid-sequenzen der kohlenhydrat-kette von N-glycopropteinen

Abstract The block synthesis starting with 3,6-di- O -acetyl-2-deoxy-2-phthalimido-4- O -(2,3,4,6-tetra- O -acetyl-β- d -galactopyranosyl)-β- d -glucopyranosyl bromide ( 2 ) to form β-glycosidic linkages has proved to be very effective for the preparation of more complex oligosaccharides. The coupling of 2 with O -(3,4,6-tri- O -benzyl-α- d -mannopyranosyl)-(1→6)- O -(3- O -allyl-2,4-di- O -benzyl-β- d -mannopyranosyl)-(1→4)-1,6- anhydro-2-azido-3- O -benzyl-2-deoxy-β- d -glucopyranose and O -(3,4,6-tri- O -benzyl-α- d -mannopyranosyl)-(1→3)- O -(6- O -acetyl-2,4-di- O -benzyl-β- d -mannopyranosyl)-(1→4)-1,6- anhydro-2-azido-3- O -benzyl-2-deoxy-β- d -glucopyranose, as well as with O -(3,4,6-tri- O -benzyl-α- d -mannopyranosyl)-(1→3)- O -[(3,4,6-tri- O -benzyl-α- d -mannopyranosyl)-(1→6)]- O -(2,4-di- O -benzyl-β- d -mannopyranosyl)-(1→4)-1,6-anhydro-2-azido-3- O -benzyl-2-deoxy-β- d -glucopyranose, afforded two pentasaccharides and one octasaccharide. The deblocking of these oligosaccharides gave O -β- d -galactopyranosyl-(1→4)- O -(2-acetamido-2-deoxy-β- d -glucopyranosyl)-(1→2)- O -α- d - mannopyranosyl-(1→6)- O -β- d -mannopyranosyl-(1→4)-2-acetamido-2-deoxy- d -glucopyranose, O -β- d -galactopyranosyl-(1→4)- O -(2-acetamido-2-deoxy-β- d -glucopyranosyl)-(1→2)- O -α- d -mannopyranosyl-(1→3)- O -β- d -mannopyranosyl-(1→4)-2-acetamido-2-deoxy- d -glucopyranose, and O -β- d -galactopyranosyl-(1→4)- O -(2-acetamido-2- deoxy-β- d -glucopyranosyl)-(1→2)- O -α- d -mannopyranosyl-(1→3)- O -[ O -β- d -galactopyranosyl-(1→4)- O -(2-acetamido-2- deoxy-β- d -glucopyranosyl)-(1→2)- O -α- d -mannopyranosyl-(1→6)]- O -β- d -mannopyranosyl-(1→4)-2-acetamido-2-deoxy- d - glucopyranose, respectively, which are fundamental structures of the carbohydrate chain of N -glycoproteins of the lactosamine type.

Synthese von unsymmetrischen pentasaccharid-sequenzen der N-glycoproteine

Abstract The two pentasaccharides O -(2-acetamido-2-deoxy-β- d -glucopyranosyl)- (1→2)- O -α- d -mannopyranosyl-(1→3)- O -[α- d -mannopyranosyl-(1→6)]- O -β- d - mannopyranosyl-(1→4)-2-acetamido-2-deoxy- d -glucopyranose and O -(2-acetamido-2-deoxy-β- d -glucopyranosyl)-(1→2)- O -α- d -mannopyranosyl-(1→6)-[ O -α- d -mannopyranosyl-(1→3)]- O -β- d -mannopyranosyl-(1→4)-2-acetamido-2-deoxy- d - glucopyranose which represent unsymmetrical sequences of the carbohydrate chain of N -glycoproteins of the lactosamine type and, thus, are useful compounds for studying the biosynthesis of N -glycoproteins, were synthesized by glycosidation of partially deprotected tetrasaccharides.