Pseudosugars, 40 - Synthesis of ether- and imino-linked octyl N-acetyl-5a '-carba-beta-lactosaminides and -isolactosaminides: Acceptor substrates foralpha-(1 -> 3/4)-fucosyltransferase, and enzymatic synthesis of 5a '-carbatrisaccharides

Synthesis of ether-linked octyl 5a'-carba-beta-lactosaminide 3 and -isolact osaminide 5 was carried out in seven steps, starting from the coupling prod ucts of 1,2-anhydro-5a-carba-beta-D-mannopyranose derivative 7, and the oxi de anions generated from the octyl N-acetyl-beta-D-glucosaminide derivative s 13 and 16, respectively, under basic conditions. The 5a-carba-alpha-D-man nopyranose residues of the coupling products 17 and 26 were transformed int o the beta-D-gluco configuration through epimerization of the respective 2' -oxo derivatives 19 and 28, and selective reduction, and then into the beta -D-galacto configuration by direct nucleophilic substitution of their 4',6' -dimesylates 23 and 31 with an acetate ion. Biological assay has shown that 3 is an acceptor substrate for human-milk alpha-(1-->3/4)-fucosyltransfera se and, interestingly, 5 is not. In addition, the imino-linked congeners 4 and 6 have been synthesized by coupling of the 4-amino;4-deoxy- and 3-amino -3-deoxy derivatives 37 and 41 of octyl N-acetyl-beta-D-glucosaminide, and the carba-sugar epoxide 13, respectively, and subsequent deprotection. Comp ound 4 is a substrate while 6 is neither a substrate nor an inhibitor for f ucosyltransferase. Small-scale enzymatic synthesis was carried out by treat ment of 3 and 4 with GDP-fucose and milk fucosyltransferase, which resulted in conversion into the corresponding trisaccharides 47 and 48, respectivel y.