2-(Hydroxycarbonyl)benzyl Glycosides:  A Novel Type of Glycosyl Donors for Highly Efficient β-Mannopyranosylation and Oligosaccharide Synthesis by Latent-Active Glycosylation

Abstract

2-(Benzyloxycarbonyl)benzyl (BCB) glycosides were prepared by coupling of the corresponding tetraacetylglycosyl bromides and benzyl 2-(hydroxymethyl)benzoate. The BCB glycosides were converted almost quantitatively into the corresponding 2-(hydroxycarbonyl)benzyl (HCB) glycosides by selective hydrogenolysis of the benzyl ester functionality without affecting the benzylidene acetal and the benzyl ether. Treatment of the HCB 4,6-O-benzylidenemannopyranoside 4 with triflic anhydride in the presence of di-tert-butylmethylpyridine and subsequent addition of the glycosyl acceptor having a primary hydroxyl group afforded exclusively the disaccharide of the beta-mannopyranosyl linkage. Glycosylation of the compound 4 with secondary and tertiary alcohols also provided beta-mannopyranosides as the major products. Glycosylation of the HCB 4,6-O-cyclohexylidenemannoside 5 with primary alcohols was also highly beta-selective, and the HCB 2,3-O-cyclohexylidenemannoside 6 exhibited the moderate beta-selectivity. On the other hand, unlike the HCB mannosides, the HCB 4,6-O-benzylideneglucoside 7 gave exclusively the disaccharides of the alpha-glycopyranosyl linkage in the glycosylation with primary alcohols. The latent BCB-disaccharide 23, which was obtained from the HCB mannoside 4 as the donor and the BCB glucoside 12 as the acceptor by the present glycosylation method, was converted into the active HCB-disaccharide 39 by selective hydrogenolysis. Repetitive glycosylation of the donor 39 with the same acceptor 12 afforded the BCB-trisaccharide 40. Other BCB-trisaccharides 42 and 46 were also efficiently synthesized by employing the present methodology.

Direct and stereoselective synthesis of β-d-mannosides using 4,6-O-benzylidene-protected mannosyl diethyl phosphite as a donor

“…18 Very recently, Crich and Chandrasekera, based on kinetic isotope effects (KIEs) measurements, proposed that the displacement of the α-mannosyl triflate by an acceptor alcohol proceeded with the development of a substantial oxocarbenium ion character. 19 The effectiveness of the intermediate was also recognized by Weingart and Schmidt 20 with the corresponding trichloroacetimidate and by Kim and co-workers 21 with the 2-(hydroxycarbonyl)benzyl 4,6-O-benzylidenemannoside.…”

Surface Glycans ofCandida albicansand Other Pathogenic Fungi: Physiological Roles, Clinical Uses, and Experimental Challenges

“…Because the ␤ anomer is less energetically favored, synthesis of ␤-linked oligosaccharides has been particularly problematic. However, several groups have recently reported effective syntheses of ␤-oligomannosides (55,160,205,206). These synthetic oligosaccharides are conjugated through their reducing end, complicating fluorophore labeling, or have protecting groups still attached to nonbonding alcohol groups.…”

Direct and Stereoselective Synthesis of β‐D‐Mannosides Using 4,6‐O‐Benzylidene‐Protected Mannosyl Diethyl Phosphite as a Donor.

“…18 Very recently, Crich and Chandrasekera, based on kinetic isotope effects (KIEs) measurements, proposed that the displacement of the α-mannosyl triflate by an acceptor alcohol proceeded with the development of a substantial oxocarbenium ion character. 19 The effectiveness of the intermediate was also recognized by Weingart and Schmidt 20 with the corresponding trichloroacetimidate and by Kim and co-workers 21 with the 2-(hydroxycarbonyl)benzyl 4,6-O-benzylidenemannoside. 22 ing group at C-2.…”