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Synthesis 2004(14): 2293-2296  
DOI: 10.1055/s-2004-831188
PAPER
© Georg Thieme Verlag Stuttgart · New York

Large-Scale Chemical and Enzymatic Synthesis of a Clostridium difficile Toxin A Binding Trisaccharide [1]

R. Murray Ratcliffe*a, Vivekanand P. Kamatha, Robert E. Yeskea, Jonathan M. Gregsona, Ying R. Fangb, Monica M. Palcic*b
a Department of Research & Process Development, SYNSORB Biotech Inc., 201, 1204 Kensington Road, Calgary, AB T2E 6J7, Canada
e-Mail: murratcliffe@pathcom.ca;
b Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada
e-Mail: monica.palcic@ualberta.ca;
Further Information

Publication History

Received 18 September 2003
Publication Date:
19 August 2004 (online)

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Abstract

Trisaccharide 1, 8-methoxycarbonyloctyl-O-(α-d-galactopyranosyl)-(1→3)-(β-d-galactopyranosyl)-(1→4)-β-d-glucopyranoside, linked to a solid support can be used to remove Clostridium difficile toxin A from the intestinal tract. Therefore, multi-gram chemical and enzymatic synthesis of the toxin binding trisaccharide 1 from 8-methoxycarbonyloctyl β-lactoside disaccharide 2 were explored. Chemical conversion in 30% overall yield could be achieved in seven steps. Alternatively a single step enzymatic conversion of the lactoside using recombinant α(1→3)-galactosyltransferase with UDP-galactose or UDP-glucose/UDP-Glc epimerase gave 1 in 85-90% yield.

Key words

Clostridium difficile toxin A - galactosyltransferase - iso-globo trisaccharide - Gal(α1,3)Gal epitope

1

Presented, in part, at the 4th Carbohydrate Bioengineering Meeting Stockholm Sweden, June 10-13, 2001.