Convergent synthesis of the hexasaccharide repeating unit of the capsular polysaccharide of Klebsiella serotype K-34

Convergent Synthesis of a Pentasaccharide Containing a Rare Sugar 4‐amino‐4‐deoxy‐D‐fucose Related to the Cell Wall O‐polysaccharide of Acinetobacter baumannii 90

“…The 4‐amino‐4‐deoxy‐α‐D‐fucopyranose moiety was incorporated in the target pentasaccharide using 4‐azido‐4‐deoxy‐α‐D‐fucopyranosyl trichloroacetimidate derivative ( 6 ) as glycosyl donor, which has been prepared following the reaction conditions reported earlier [18] from D‐galactose. Preparation of ethyl 3‐ O ‐acetyl‐6‐ O ‐benzyl‐2‐deoxy‐4‐ O ‐levulinyl‐2‐phthalimido‐1‐thio‐β‐D‐galactopyranoside ( 7 ) was achieved in 45 % over all yield from ethyl 3‐ O ‐acetyl‐6‐ O ‐benzyl‐2‐deoxy‐2‐phthalimido‐1‐thio‐β‐D‐glucopyranoside ( 4 ) following a three step reaction sequence involving (a) treatment with triflic anhydride in the presence of pyridine; (b) treatment of the triflate derivative with sodium nitrite via S N 2 reaction followed by hydrolysis of the nitrite derivative [19] and (c) treatment of the free hydroxyl group with levulinic acid in the presence of a combination of N , N′ ‐diisopropylcarbodiimide (DIC) and DMAP [26] .…”

“…Therefore, monosaccharide synthons 2 , [14] 3 , [15] 4 , [16] 5 , [17] 6 [18] were prepared in very good yield following the synthetic methodologies reported earlier (Figure 1). The noteworthy features of the synthetic strategy includes, (a) synthesis of a pentasaccharide containing a rare sugar, 4‐amino‐4‐deoxy‐α‐D‐fucopyranose moiety; (b) stereoselective [3+2] block glycosylation of trisaccharide acceptor with disaccharide thioglycoside donor; (c) preparation of D‐galactosamine derivative from D‐glucosamine derivative [19] ; (d) stereoselective 1,2‐ cis glycosylation of D‐galactopyranosyl thioglycoside donor using a combination of copper(II) bromide and tetre‐ n ‐butylammonium bromide (TBAB) as thiophilic activator in a mixed solvent 1,2‐dichloroethane‐DMF (5 : 1) [20] ; (e) orthogonal glycosylation [21] of 4‐azido‐4‐deoxy‐α‐D‐fucopyranosyl trichloroacetimidate derivative [18] with D‐galactopyranosyl thioglycoside acceptor; (f) use of perchloric acid supported over silica (HClO 4 ‐SiO 2 ) [22] for the activation of glycosyl trichloroacetimidate derivative [23] and (g) removal of benzyl ether and benzylidene acetal in a catalytic transfer hydrogenation condition using triethylsilane as the source of hydrogen [24] . The PMP group at the anomeric centre at the reducing end can be easily removed [25] under an oxidative reaction condition to provide pentasaccharide hemiacetal derivative, which can be conjugated to a suitable protein following standard reaction condition to generate glycoconjugate derivative.…”

“…The retrosynthetic strategy revealed that the target pentasaccharide 1 can be synthesized by a stereoselective [3 + 2] block glycosylation of a trisaccharide acceptor and a disaccharide thioglycoside donor, which can be synthesized from suitably functionalized monosaccharide intermediates. Therefore, monosaccharide synthons 2, [14] 3, [15] 4, [16] 5, [17] 6 [18] were prepared in very good yield following the synthetic methodologies reported earlier (Figure 1). The noteworthy features of the synthetic strategy includes, (a) synthesis of a pentasaccharide containing a rare sugar, 4-amino-4-deoxy-α-Dfucopyranose moiety; (b) stereoselective [3 + 2] block glycosylation of trisaccharide acceptor with disaccharide thioglycoside donor; (c) preparation of D-galactosamine derivative from Dglucosamine derivative [19] ; (d) stereoselective 1,2-cis glycosylation of D-galactopyranosyl thioglycoside donor using a combination of copper(II) bromide and tetre-n-butylammonium bromide (TBAB) as thiophilic activator in a mixed solvent 1,2dichloroethane-DMF (5 : 1) [20] ; (e) orthogonal glycosylation [21] of 4-azido-4-deoxy-α-D-fucopyranosyl trichloroacetimidate derivative [18] with D-galactopyranosyl thioglycoside acceptor; (f) use of perchloric acid supported over silica (HClO 4 -SiO 2 ) [22] for the activation of glycosyl trichloroacetimidate derivative [23] and (g) removal of benzyl ether and benzylidene acetal in a catalytic transfer hydrogenation condition using triethylsilane as the source of hydrogen.…”

Synthesis of the Pentasaccharide of the K14 Capsular Polysaccharide of Antibiotic Resistant ST25 Acinetobacter baumannii isolate, D46 and O‐Polysaccharide of Acinetobacter baumannii O11

“…In order to obtain desired oligosaccharides with conserved structural integrity, development of chemical synthetic strategy would be the best alternative approach. [15] The synthetic oligosaccharides can be easily conjugated with suitable protein to give glycoconjugate derivatives for their biological/immunochemical study to determine the efficacy to act as vaccine leads. [16] During the recent past, a variety of semisynthetic glycoconju-gate derivatives have been developed for their use as antibacterial vaccine candidates.…”