Convergent syntheses of LeX analogues

• Published in: Beilstein journal of organic chemistry Vol. 6; no. 1; p. 17
• Main Authors: Wang, An, Hendel, Jenifer, Auzanneau, France-Isabelle
• Format: Journal Article
• Language: English
• Published: Trakehner Str. 7-9, 60487 Frankfurt am Main, Germany Beilstein-Institut 22.02.2010
• Subjects: Birch reduction; Chemistry; convergent synthesis; desulfurization; Full Research Paper; Lewis X
• ISSN: 1860-5397; 1860-5397
• DOI: 10.3762/bjoc.6.17

The synthesis of three Le x derivatives from one common protected trisaccharide is reported. These analogues will be used respectively for competitive binding experiments, conjugation to carrier proteins and immobilization on gold. An N -acetylglucosamine monosaccharide acceptor was first glycosylated at O-4 with a galactosyl imidate. This coupling was performed at 40 °C under excess of BF 3 ·OEt 2 activation and proceeded best if the acceptor carried a 6-chlorohexyl rather than a 6-azidohexyl aglycon. The 6-chlorohexyl disaccharide was then converted to an acceptor and submitted to fucosylation yielding the corresponding protected 6-chlorohexyl Le x trisaccharide. This protected trisaccharide was used as a precursor to the 6-azidohexyl, 6-acetylthiohexyl and 6-benzylthiohexyl trisaccharide analogues which were obtained in excellent yields (70–95%). In turn, we describe the deprotection of these intermediates in one single step using dissolving metal conditions. Under these conditions, the 6-chlorohexyl and 6-azidohexyl intermediates led respectively to the n -hexyl and 6-aminohexyl trisaccharide targets. Unexpectedly, the 6-acetylthiohexyl analogue underwent desulfurization and gave the n -hexyl glycoside product, whereas the 6-benzylthiohexyl analogue gave the desired disulfide trisaccharide dimer. This study constitutes a particularly efficient and convergent preparation of these three Le x analogues.