745032-76-2Relevant academic research and scientific papers
New nonhydrolyzable mimetics of sialyl Lewis x and their binding affinity to P-selectin
Carrel, Frederic,Giraud, Sylvain,Spertini, Olivier,Vogel, Pierre
, p. 1048 - 1070 (2007/10/03)
Wittig olefination of (2S,3R,5S,6R)-5-(acetyloxy)-tetrahydro-6- [(methoxymethoxy)methyl]-3-(phenylthio)-2H-pyran-2-acetaldehyde ((+)-10) with {2-[(2S,3R,4R,5R,6S)-tetrahydro-3,4,5-tris(methoxymethoxy)-6-methyl-2H-pyran-2- yl]ethyl}triphenylphosphonium iodide ((-)-11) gave a (Z)-alkene derivative (+)-12 that was converted into (αR,2R,3S,4R,5R,6S)-tetrahydro-α,3- dihydroxy-2-(hydroxymethyl)-5-(phenylthio)-6-((2Z)-4-[(2S,3S,4R,5S,6S) -tetrahydro-3,4,5-trihydroxy-6-methyl-2H-pyran-2-yl]but-2-enyl) 2H-pyran-4-acetic acid (8), (αR,2R,3S,4R,6S)-tetrahydro-α,3- dihydroxy-2-(hydroxymethyl)-6-(4-[(2S,3S,4R,5S,6S)-tetrahydro-3,4, 5-trihydroxy-6-methyl-2H-pyran-2-yl]butyl}-2H-pyran-4-acetic acid (9), and simpler analogues without the hydroxy-acetic side chain such as (2S,3S,4R,5S,6S)-tetrahydro-6-methyl-2-[(2Z)-4-[(2S,3R,5S,6R) -tetrahydro-5-hydroxy-6-(hydroxymethyl)-3-(phenylthio)-2H-pyran-2-yl}but-2-enyl} -2H-pyran-3,4,5-triol (30), (2S,3S,4R,5S,6S)-tet-rahydro-6-methyl-2-{[(2S,5S,6R) -tetrahydro-5-hydroxy-6-(hydroxymethyl)-2H-pyran-2-yllbutyl}-2H-pyran-3,4, 5-triol ((-)-41) and (2S,3S,4R,5S,6S)-tetrahydro-6-methyl-2-1(2Z/E))-4-[(2R,5S, 6R)-tetrahydro-5-hydroxy-6-(hydroxymethyl)-2H-pyran-2-yl]but-2-enyl}-2H-pyran-3, 4,5-triol (43). The key intermediates (+)-10 and (-)-11 were derived from isolevoglucosenone and from L-fucose, respectively. The following IC 50 values were measured in a ELISA test for the affinities of sialyl Lewis x tetrasaccharide, 8, 9, 30, (-)-41, and 43 toward P-selectin: 0.7, 2.5-2.8, 7.3-8.0, 5.3-5.9, 5.0-5.2, and 3.4-4.1 mM, respectively.
