Synthesis of ether-linked octyl 5aЈ-carba-β-lactosaminide 3 substrate for human-milk α-(1Ǟ3/4)-fucosyltransferase and, interestingly, 5 is not. In addition, the imino-linked and -isolactosaminide 5 was carried out in seven steps, starting from the coupling products of 1,2-anhydro-5a-carba-congeners 4 and 6 have been synthesized by coupling of the 4-amino-4-deoxy-and 3-amino-3-deoxy derivatives 37 and β-D-mannopyranose derivative 7, and the oxide anions generated from the octyl N-acetyl-β-D-glucosaminide 41 of octyl N-acetyl-β-D-glucosaminide, and the carba-sugar epoxide 8, respectively, and subsequent deprotection. derivatives 13 and 16, respectively, under basic conditions. The 5a-carba-α-D-mannopyranose residues of the coupling Compound 4 is a substrate while 6 is neither a substrate nor an inhibitor for fucosyltransferase. Small-scale enzymatic products 17 and 26 were transformed into the β-D-gluco configuration through epimerization of the respective 2Ј-oxo synthesis was carried out by treatment of 3 and 4 with GDPfucose and milk fucosyltransferase, which resulted in derivatives 19 and 28, and selective reduction, and then into the β-D-galacto configuration by direct nucleophilic conversion into the corresponding trisaccharides 47 and 48, respectively. substitution of their 4Ј,6Ј-dimesylates 23 and 31 with an acetate ion. Biological assay has shown that 3 is an acceptor
In recent years, some human α-(1Ǟ3/4)-fucosyltransfer-to enzymatic hydrolysis, they should be useful for a transferase assay or in cell-uptake experiments to study oligosac-ases have been extensively studied [3] since they are involved in the last steps of the biosynthesis of Lewis oligosaccharide charide biosynthesis, provided they are substrates for fucosyltransferases. These disaccharide mimetics have therefore antigens. These antigens include sialyl Lewis x, which is a tumor-associated structure and a ligand of E-selectin-me-been considered as substrates and inhibitors for the Lewis α-(1Ǟ3/4)-fucosyltransferase available from human milk. diated inflammatory processes. [4] There is interest in developing assays for monitoring enzyme activity and specific fucosyltransferase inhibitors which prevent the synthesis of these antigens. These inhibitors would represent potential Results and Discussion anti-inflammatory or anti-tumor agents. [5] Previously, we described [6] that the carbatrisaccharide β-Synthesis of Ether-Linked Octyl -GlcpNAc-(1Ǟ2)-5a-carba-α--Manp-(1Ǟ6)-β--GlcpO-5aЈ-Carbalactosaminide (3) and -isolactosaminide (5) (CH 2 ) 7 CH 3 was shown to act as a structurally minimum substrate analog for enzyme N-(acetylglucosaminyl)-Octyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β--glucopyranoside (9) was prepared [7] in 44% yield from -glucosatransferase-V, the kinetic parameters being comparable to those of the parent trisaccharide. This paper describes the mine hydrochloride by subsequent per-N,O-acetylation, and then glycosylation with octanol and ferric chloride in di-synthesis of pseudo-N-acetyllactosaminides 3 and 4, andisolactosaminides 5 and 6, where the β--galactopyranose chloromethane. Zemple ´n de-O-acetylation [8] of 9, followed by benzylidenation with benzaldehyde in the presence of moieties of the true substrates 1 and 2 are replaced by etherand imino-linked 5a-carba-β--galactopyranose residues, zinc chloride, gave the (R)-4,6-O-benzylidene derivative [9] 10 in 88% yield. Benzylation of 10 with benzyl bromide and respectively. [6] Since these carbadisaccharides are resistant sodium hydride in DMF gave the 3-O-benzyl derivative [9] 11 (82%), which was selectively reduced with sodium cyano-[ ] Part 39: Ref. [2] [a] Department of Applied Chemistry, Faculty of Science and borohydride in THF to afford the 3,6-di-O-benzyl deriva-