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

Abstract

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.

Biosynthesis and Biological Activity of Carbasugars

“…Therefore, an area of interest is the design of potential inhibitors of these enzymes involved in the assembly of the sialyl Lewis-x structure. In the search for inhibitors of the biosynthesis of Lewis oligosaccharide antigens, the synthesis of carbasugar analogues of the disaccharide fragment highlighted in Figure 33 was carried out by Ogawa et al [413,414]. They prepared ether-and imine-linked N-acetyl-5a -carba--lactosaminides and -isolactosaminides and tested them against fucosyltransferases.…”