Synthesis of the Tetrasaccharide Repeating Unit of the β-Kdo-Containing Exopolysaccharide from Burkholderia pseudomallei and B. cepacia Complex

Abstract

The synthesis of the repeating unit of the immunogenic β-Kdo-containing exopolysaccharide produced by Burkholderia pseudomallei and bacteria of the B. cepacia complex is described. The target tetrasaccharide was synthesized via stereoselective 1,2-cis- and 1,2-trans-galactosylations and β-Kdosylation. A [3 + 1] coupling reaction between a trigalactosyl N-phenyl-2,2,2-trifluoroacetimidate donor and a Kdo acceptor has been successfully achieved for the assembly of the tetrasaccharide skeleton.

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

“…It was suggested that the bulky DTBS group is shielding the β-face and thereby preventing attack from that face of the oxocarbenium ion. This methodology has been applied to the synthesis of glycolipids and was shown to also work with 2- O -benzyl [ 56 ] or 2- O -TBS and with N -phenyltrifluoroacetimidate as the leaving group [ 57 – 58 ]. A somewhat similar influence has been observed with the much less steric demanding 4,6- O -benzylidene protective group [ 59 ].…”

Recent Developments in the Use of Flow Hydrogenation in the Field of Medicinal Chemistry

“…Product References [30] CBz protecting group 20% Pd(OH) 2 /C; 45°C, 10 bar, 1.0 mL min −1 , 1 cycle; 67% [31] Benzyl protecting group 10% Pd/C; 65°C, full H 2 mode, 1.0 mL min −1 , 1 cycle; 60% [32] Benzoyl protecting group [56] Phthalimide protecting group 10% Pd/C; 50°C, 1 bar, 50°C, 0.5 mL min -1 ; 56-81% [57] Cbz protecting group 10% Pd/C; RT, 1 bar, 50°C, 1.0 mL min −1 ; 99%; 97% ee Table 3. Flow reduction and removal of protecting groups.…”

Progress in Kdo-glycoside chemistry

“…Kdo thioglycoside donors allow for various activation protocols using thiophilic promoters, but are susceptible to pronounced elimination reactions with less reactive glycosyl acceptors. These donors have mainly been applied for the preparation of spacer glycosides, in particular of those with a β-anomeric configuration 32,33. In 2007, Oscarson et al published a detailed and systematic model study with several Kdo thioglycoside donors equipped with acetyl, benzoyl and isopropylidene protecting groups in different solvents and with variations of reaction temperature and activating agents such as dimethyl(methylthio)sulfonium trifalte (DMTST), NIS/AgOTf, NIS and IBr 34.…”