Large-scale chemical and chemo-enzymatic synthesis of a spacer-containing Pk-trisaccharide

• Published in: Carbohydrate research Vol. 339; no. 6; pp. 1141 - 1146
• Main Authors: Kamath, Vivekanand P, Yeske, Robert E, Gregson, Jonathan M, Ratcliffe, R.Murray, Fang, Ying R, Palcic, Monica M
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 28.04.2004; Elsevier
• Subjects: Acetic Acid - chemistry; Biochemistry & Molecular Biology; Carbohydrate Conformation; Carbohydrate Sequence; Chemistry; Chemistry, Applied; Chemistry, Organic; Chemoenzymatic; Galactosides - chemistry; Galactosyltransferases - metabolism; Lactose - chemistry; Life Sciences & Biomedicine; Ligands; Molecular Sequence Data; Oligosaccharides - chemistry; Physical Sciences; Pk-trisaccharide; Science & Technology; Trisaccharides - chemistry; Uridine Diphosphate Galactose - chemistry; Pk-trisaccharide; Chemoenzymatic; ALPHA-D-GALACTOPYRANOSYL; CELL-SURFACE GLYCANS; FABRYS-DISEASE; GLOBOPENTAOSYL CERAMIDE; ESCHERICHIA-COLI; BENZYLIDENE ACETALS; ENZYMATIC-SYNTHESIS; SELECTIN-CARBOHYDRATE INTERACTIONS; STEREOCONTROLLING AUXILIARY; chemoenzymatic; POSITIONAL ISOMER
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2003.12.027

Graphic The Pk-trisaccharide, linked to a solid carrier, is a potential agent for neutralization of shiga-like toxin in the gastrointestinal tract. Two approaches to the multigram-scale synthesis of a linkable Pk-trisaccharide derivative were therefore investigated. A four-step chemical synthesis yielded 8-methoxycarbonyloctyl β-lactoside in 75% yield from lactose. Further conversion of this derivative through either multistep organic synthesis or one-step enzymatic galactosylation with UDP-galactose and recombinant α-1,4-galactosyltransferase gave the Pk-trisaccharide derivative 8-methoxycarbonyloctyl α- d-galactopyranosyl-(1 → 4)-β- d-galactopyranosyl-(1 → 4)-β- d-glucopyranoside in 25% and 68% overall yields from commercial lactose, respectively.