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

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 beta-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 alpha-1,4-galactosyltransferase gave the Pk-trisaccharide derivative 8-methoxycarbonyloctyl alpha-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranoside in 25% and 68% overall yields from commercial lactose, respectively.