Synthesis of Carbon‐Backbone‐Elongated GDP‐L‐Fucose Derivatives as Substrates for Fucosyltransferase‐Catalysed Reactions

Abstract

AbstractStarting from the 6‐O‐tert‐butyldimethysilyl‐2,3;4,5‐di‐O‐isopropylidene‐D‐galactose diethyl dithioacetal (4) and proceeding through a Wittig reaction and Swern oxidation, a series of L‐fucose analogues, which unlike the normal L‐fucose possess an extended alkyl‐chain at C‐5, can be produced. The elongated carbon backbone in the L‐fucitols (22–25) as well as in the L‐fucose derivatives (30–33) increases the hydrophobic nature of the sugar molecule, promoting liquid‐crystalline properties in both series. The further derivatization of the L‐fucose analogues 30, 31 leads to the corresponding β‐L‐galacto‐deco‐ and dodeco‐pyranosyl phosphates 46, 47 and, in turn, to the respective pyranosyl guanosine 5‐diphosphates 48, 49. The reaction of the β‐L‐galactopyranosyl guanosine 5‐diphosphate 48 with 8‐methoxycarbonyloctyl 2‐acetamido‐2‐deoxy‐4‐O‐(β‐D‐galactopyranosyl)‐β‐D‐glucopyranoside (50) in the presence of a 3/4‐α‐fucosyltransferase furnished an O‐glycosidic linkage of the α‐L‐galactopdecopyranose 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 α‐fucosyltransferases.