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

Starting 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.