SYNTHESIS OF CARBON-BACKBONE-ELONGATED GDP-L-FUCOSE DERIVATIVES AS SUBSTRATES FOR FUCOSYL-TRANSFERASE-CATALYZED REACTIONS

Starting from the ethylsilyl-2,3;4,5-di-O-isopropylidene-D-galactose d iethyl dithioacetal (4) and proceeding through a Wittig reaction and S wern oxidation, a series of L-fucose analogues, which unlike the norma l L-fucose possess an extended alkyl-chain at C-5, can be produced. Th e elongated carbon backbone in the L-fucitols (22-25) as well as in th e L-fucose derivatives (30-33) increases the hydrophobic nature of the sugar molecule, promoting liquid-crystalline properties in both serie s. The further derivatization of the L-fucose analogues 30, 31 leads t o the corresponding beta-L-galacto-deco- and dodeco-pyranosyl phosphat es 46, 47 and, in turn, to the respective pyranosyl guanosine 5-diphos phates 48, 49. The reaction of the beta-L-galactopyranosyl guanosine 5 -diphosphate 48 with 8-methoxycarbonyloctyl O-(beta-D-galactopyranosyl )-beta-D-glucopyranoside (50) in the presence of a 3/4-alpha-fucosyltr ansferase furnished an O-glycosidic linkage of the alpha-L-galactopdec opyranose 30 at the 3-O-position of the N-acetyllactosamine glycoside 50. The chemo-enzymatic coupling reaction proves that the synthesized carbon-backbone-elongated L-galactopyranosyl guanosine 5-diphosphates are suitable substrates for the alpha-fucosyltransferases.