Abstract
Wittig olefination of (2__S__,3__R__,5__S__,6__R__)‐5‐(acetyloxy)‐tetrahydro‐6‐[(methoxymethoxy)methyl]‐3‐(phenylthio)‐ 2__H__‐pyran‐2‐acetaldehyde ((+)‐10) with {2‐[(2__S__,3__R__,4__R__,5__R__,6__S__)‐tetrahydro‐3,4,5‐tris(methoxymethoxy)‐6‐methyl‐ 2__H__‐pyran‐2‐yl]ethyl}triphenylphosphonium iodide ((−)‐11) gave a (Z)‐alkene derivative (+)‐12 that was converted into (αR,2__R__,3__S__,4__R__,5__R__,6__S__)‐tetrahydro‐α,3‐dihydroxy‐2‐(hydroxymethyl)‐5‐(phenylthio)‐6‐{(2__Z__)‐4‐[(2__S__,3__S__,4__R__,5__S__,6__S__)‐tetrahydro‐3,4,5‐trihydroxy‐6‐methyl‐2__H__‐pyran‐2‐yl]but‐2‐enyl}2__H__‐pyran‐4‐acetic acid (8), (αR,2__R__,3__S__,4__R__,6__S__)‐tetrahydro‐α,3‐dihydroxy‐2‐(hydroxymethyl)‐6‐{4‐[(2__S__,3__S__,4__R__,5__S__,6__S__)‐tetrahydro‐3,4,5‐trihydroxy‐6‐methyl‐2__H__‐pyran‐2‐yl]butyl}‐2__H__‐pyran‐4‐acetic acid (9), and simpler analogues without the hydroxyacetic side chain such as (2__S__,3__S__,4__R__,5__S__,6__S__)‐tetrahydro‐6‐methyl‐2‐{(2__Z__)‐4‐[(2__S__,3__R__,5__S__,6__R__)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐3‐(phenylthio)‐2__H__‐pyran‐2‐yl]but‐2‐enyl}‐2__H__‐pyran‐3,4,5‐triol (30), (2__S__,3__S__,4__R__,5__S__,6__S__)‐tetrahydro‐6‐methyl‐2‐{[(2__S__,5__S__,6__R__)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2__H__‐pyran‐2‐yl]butyl}‐2__H__‐pyran‐3,4,5‐ triol ((−)‐41) and (2__S__,3__S__,4__R__,5__S__,6__S__)‐tetrahydro‐6‐methyl‐2‐{(2__Z__/E))‐4‐[(2__R__,5__S__,6__R__)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2__H__‐pyran‐2‐yl]but‐2‐enyl}‐2__H__‐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.