The stereodirecting effect of C5-ester functions on the glycosylation stereoselectivity of 3-deoxy-d- manno-oct-2-ulosonic acid (Kdo) ethyl thioglycoside donors is presented. The coupling of 5- O-arylcarbonyl or acetyl protected Kdo thioglycosides with acceptors proceeds in an α-selective and high-yielding manner, leading to formation of α-linked Kdo glycosides products. On the other hand, the glycosylation stereoselectivity of the 5- O-2-quinolinecarbonyl (Quin) or 4-nitropicoloyl substituted Kdo thioglycoside donors is switchable: (1) The glycosylation of the 5- O-Quin carrying Kdo donors with primary glycosyl acceptors shows complete β-stereoselectivity, furnishing the corresponding β-glycosides in good-to-excellent yield. (2) The stereochemical outcome of the secondary acceptors with these Kdo donors is determined mainly by the stereoelectronic nature of the acceptor. Only or predominant α anomeric products are obtained when the Kdo donors couple with the disarmed or highly crowded secondary carbohydrate acceptors, while the selectivity may switch to predominant β in the glycosylation of the 5- O-4-nitropicoloyl carrying donor with more reactive secondary alcohols. The synthetic use of the newly developed Kdo donors 1c and 7b has been demonstrated by facile preparation of a structurally unique trisaccharide motif 19 which possesses both α- and β-Kdo glycosidic bonds.

An efficient α-sialylation methodology for various primary, secondary, and tertiary alcohol acceptors has been developed. The sialic acid ethyl thioglycoside 1b, bearing a 4-nitropicoloyl moiety as the stereodirecting group at the C4 position, was utilized as the glycosyl donor, and the sialylation reaction was activated with N-iodosuccinimide and catalytic triflic [a] 576 c with model acceptor molecule, the galactose 3,4-diol 2, [11] was carried out under the promotion of NIS (1.5 equiv.) and a catalytic amount of TfOH (0.1 equiv.) reagent system at -78 to -30°C using CH 2 Cl 2 or CH 2 Cl 2 /CH 3 CN (1:1, v/v) as solvent, and the results are summarized in Table 1. First, we examined the sialylation between picoloylated 1a and 2 in different solvents. When performed in CH 2 Cl 2 , the glycosylation gave rise to the desired (2,3)-linked sialoside product 3a in only 20 % yield with very low diastereoselectivity (α/ , 2:1), along with 87 % yield of elimination by-product 4a (Table 1, entry 1). The stereochemistry of the obtained sialoside products was confirmed by the measurement of the long-range coupling constant 3 J C1-H3ax of the sialic acid residue. [12] We were pleased to find that when CH 2 Cl 2 /CH 3 CN (1:1) was used as solvent, both the sialylation yield and selectivity were enhanced (40 %, α/ 6:1, entry 2). [13] So, using CH 2 Cl 2 /CH 3 CN (1:1) as solvent, we next studied the sialylations of donors 1b,c with 2. As a result, the product yield and selectivity obtained in the sialylation of the 4-O-4-nitropicoloyl 1b were much higher than those obtained in the condensation of the 4-O-picoloyl counterpart 1a (56 %, α/ 15:1, entry 3 vs. 40 %, α/ 6:1, entry 2), which suggests that 1b is more reactive and α-selective than 1a. On the other hand, the sialylation of the 4-O-Bz substituted 1c with 2 exhibited poor Eur. J. Org. Chem. 2020, 575-585 www.eurjoc.org

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2!5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via αstereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.

Ac onvenient and divergenta pproach was developed to prepare diverse bacterial 3-deoxy-d-manno-oct-2ulosonic acid (Kdo) oligosaccharides containing aK do-a-(2!4)-Kdo fragment. The orthogonal protected a-(2!4) linked Kdo-Kdo disaccharide 3,s erving as ac ommon precursor,w as divergently transformed into the corresponding 8-, 8'-, and4 '-hydroxy disaccharides 5, 7,a nd 14,r espectively.Then, these alcohols were glycosylated, respectively,w ith the 5,7-O-di-tert-butylsilylene (DTBS) protected Kdo thioglycoside donors 1 or 2 in an a-stereoselective and high-yielding manner to afford ar ange of Kdo oligosaccharides. Finally,r emoval of all protecting groupso ft he newly formed glycosides resulted in the desired freeK do oligomer.

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2!5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via αstereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.