Unexpected stereochemical outcome of activated 4,6-O-benzylidene derivatives of the 2-deoxy-2-trichloroacetamido-D-galacto series in glycosylation reactions during the synthesis of a chondroitin 6-sulfate trisaccharide methyl glycoside.
The synthesis of methyl (beta-D-glucopyranosyluronic acid)-(1-->3)-(2-acetamido-2-deoxy-6-O-sulfonato-beta-D-galactopyr anosyl)-(1-->4)-(beta-D-glucopyranosid)uronate trisodium salt, a chondroitin 6-sulfate trisaccharide derivative, is described. Loss of stereocontrol in glycosylation reactions involving activated 4,6-O-benzylidene derivatives of the 2-deoxy-2-trichloroacetamido-D-galacto series and D-glucuronic acid-derived acceptors was highlighted. This draw-back was overcome through the use of phenyl 3,4,6-tri-O-acetyl-2-deoxy-1-thio-2-trichloroacetamido-beta-D-gala ctopyranoside, which afforded the desired beta-linked disaccharide derivative in high yield with an excellent stereoselectivity. This later was submitted to acid-catalyzed methanolysis, followed by benzylidenation, and condensed with methyl 2,3,4-tri-O-benzoyl-1-O-trichloroacetimidoyl-alpha-D-glucopyran uronate to afford the expected trisaccharide derivative. Subsequent transformation of the N-trichloroacetyl group into N-acetyl, mild acid hydrolysis, selective O-sulfonation at C-6 of the amino sugar moiety, and saponification afforded the target molecule as its sodium salt in high yield.
Bélot
F
F
Institut de Chimie Organique et Analytique, UPRES-A CNRS 6005, UFR Faculté des Sciences, Université d'Orleans, France.
Jacquinet
J C
JC
D002240:Carbohydrate Sequence; D002809:Chondroitin Sulfates / Q000138:chemical synthesis* / Q000737:chemistry*; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008969:Molecular Sequence Data; D013237:Stereoisomerism; D014312:Trisaccharides / Q000737:chemistry*
D014312:Trisaccharides; C410289:chondroitin 6-sulfate trisaccharide methyl glycoside; D002809:Chondroitin Sulfates