title: Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors.
abstract: In this article a series of divalent and trivalent carbohydrate mimetics on the basis of an enantiopure aminopyran and of serinol is described. These aminopolyols are connected by amide bonds to carboxylic acid derived spacer units either by Schotten-Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3·DMF complex was optimized. It was crucial to follow this process by 700 MHz (1)H NMR spectroscopy to ensure full conversion and to use a refined neutralization and purification protocol. Many of the compounds could not be tested as L-selectin inhibitor by SPR due to their insolubility in water, nevertheless, a divalent and a trivalent amide showed surprisingly good activities with IC50 values in the low micromolar range.
authors.affiliation: Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, D-14195 Berlin, Germany.
authors.forename: Joana
authors.initials: J
authors.lastname: Salta
authors.affiliation: Charité Universitätsmedizin Berlin, Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Campus Virchow Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dernedde
authors.affiliation: Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, D-14195 Berlin, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Reissig
keywords: aminopolyols; carbohydrate mimetics; carboxylic acid amides; inhibition; multivalency; selectins; sulfation