Collect. Czech. Chem. Commun. 2006, 71, 1659-1672

Synthesis of D-Galactopyranosylphosphonic and (D-Galactopyranosylmethyl)phosphonic Acids as Intermediates of Inhibitors of Galactosyltransferases

Helena Heissigerováa, Petr Kočalkaa, Martina Hlaváčkováa, Anne Imbertyb, Christelle Bretonb, Valerie Chazaletb and Jitka Moravcováa,*

a Department of Chemistry of Natural Compounds, Institute of Chemical Technology, Prague, 166 28 Prague 6, Czech Republic
b Centre de Recherches sur les Macromolecules Végétales, CNRS (affiliated with Université Joseph Fourier), 601 rue de la Chimie, BP 53, 38041 Grenoble cedex 9, France


Employing the Michaelis-Arbuzov reaction of 1-O-acetyl-2,3,4,6-tetra-O-benzyl-D-galactopyranose with triethyl phosphite and trimethylsilyl trifluoromethanesulfonate, α- and β-D-galactopyranosylphosphonic acids were prepared in 33 and 28% yields, respectively. (α-D-Galactopyranosylmethyl)phosphonic acid was synthesized by a five-step route from 2,3,4,6-tetra-O-benzyl-D-galactopyranose in 52% overall yield. When tested against bovine α-1,3- and β-1,4-galactosyltransferases, all three compounds showed, at best, very poor inhibitions. Both enzymes were inhibited more effectively by β-D-galactopyranosylphosphonic acid (IC50 = 17 mmol l-1 at 13.5 μmol l-1 of UDP-Gal for β4GalT).

Keywords: Carbohydrates; UDP-Gal; Michaelis-Arbuzov reaction; Phosphonates; Galactosyltransferases; C-Glycosides.

References: 25 live references.