Synthesis of Ether‐ and Imino‐Linked Octyl N ‐Acetyl‐5a′‐carba‐β‐lactosaminides and ‐isolactosaminides: Acceptor Substrates for α‐(1→3/4)‐Fucosyltransferase, and Enzymatic Synthesis of 5a′‐Carbatrisaccharides

Synthesis of ether‐linked octyl 5a′‐carba‐β‐lactosaminide 3 and ‐isolactosaminide 5 was carried out in seven steps, starting from the coupling products of 1,2‐anhydro‐5a‐carba‐β‐ D ‐mannopyranose derivative 7 , and the oxide anions generated from the octyl N ‐acetyl‐β‐ D ‐glucosaminide derivatives 13 and 16 , respectively, under basic conditions. The 5a‐carba‐α‐ D ‐mannopyranose residues of the coupling products 17 and 26 were transformed into the β‐ D ‐ gluco configuration through epimerization of the respective 2′‐oxo derivatives 19 and 28 , and selective reduction, and then into the β‐ 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 α‐(1→3/4)‐fucosyltransferase 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‐β‐ D ‐glucosaminide , and the carba‐sugar epoxide 8 , respectively, and subsequent deprotection. Compound 4 is a substrate while 6 is neither a substrate nor an inhibitor for fucosyltransferase. Small‐scale enzymatic synthesis was carried out by treatment of 3 and 4 with GDP‐fucose and milk fucosyltransferase, which resulted in conversion into the corresponding trisaccharides 47 and 48 , respectively.