Synthesis of a Pentasaccharide Fragment Related to the Inner Core Region of Rhizobial and Agrobacterial Lipopolysaccharides

Abstract

The pentasaccharide fragment α-d-Man-(1 → 5)-[α-d-Kdo-(2 → 4)-]α-d-Kdo-(2 → 6)-β-d-GlcNAc-(1 → 6)-α-d-GlcNAc equipped with a 3-aminopropyl spacer moiety was prepared by a sequential assembly of monosaccharide building blocks. The glucosamine disaccharide—as a backbone surrogate of the bacterial lipid A region—was synthesized using an 1,3-oxazoline donor, which was followed by coupling with an isopropylidene-protected Kdo-fluoride donor to afford a protected tetrasaccharide intermediate. Eventually, an orthogonally protected manno-configured trichloroacetimidate donor was used to achieve the sterically demanding glycosylation of the 5-OH group of Kdo in good yield. The resulting pentasaccharide is suitably protected for further chain elongation at positions 3, 4, and 6 of the terminal mannose. Global deprotection afforded the target pentasaccharide to be used for the conversion into neoglycoconjugates and “clickable” ligands.

Synthesis of an Undecasaccharide Featuring an Oligomannosidic Heptasaccharide and a Bacterial Kdo-lipid A Backbone for Eliciting Neutralizing Antibodies to Mammalian Oligomannose on the HIV-1 Envelope Spike

“…The donor was formed by a first coupling step of the known α-(1→2)-connected trichloroacetimidate 18 (28) with the orthogonally protected primary alcohol 19 . Thioglycoside 19 was prepared according to the literature 16,29 and was equipped with a 3- O -naphthylmethyl protecting group, which could eventually also serve for incorporation of the D2 arm. Glycosylation of 19 was promoted by catalytic TMSOTf at room temperature in dichloromethane and afforded the α-(1→6)-linked mannotrioside 20 in 72% yield (Scheme 4).…”

“…Finally, saponification of the methyl ester groups in aqueous NaOH led to the fully deprotected undecasaccharide 24 isolated in 43% yield for the last three steps after HILIC purification. A full assignment of the deprotected undecasaccharide 24 suffered from severe overlap of signals, but key assignments could still be achieved, and furthermore, superposition of HSQC spectra with octasaccharide 9 , the previously synthesized core pentasaccharide 16 ManKdo 2 GlcNAc 2 and the 3-aminopropyl mannoheptaoside fragment 13 allowed for cross-checking the NMR assignments. Specifically, an HMBC correlation of the anomeric proton at 4.89 of mannose unit E to a downfield shifted methylene carbon of mannose A at 65.9 ppm was observed, confirming position 6 as the linkage site of the D3 arm.…”

Recent progress in chemical synthesis of bacterial surface glycans

“…Synthetic targets chemically obtained include repeating units (RUs) and related oligomers or analogs of CPSs (1-25) [10,12,[19][20][21][22][23][24][25][26][46][47][48][49][50][51][52][53][54][55][56][57][58][59], LPSs and LOSs [28][29][30][31][32][33][34][35][36][37][60][61][62][63][64][65][66][67][68][69][70][71][72], cell wall polysaccharides (50)(51)(52)(53)…”

“…The LPS and LOS oligosaccharides and analogs obtained (Figure 2B) include those from B. pertussis (26) [60] ** ; P. aeruginosa STO11 (27) [61] ** ; P. shigelloide ST51 (28) [62]; B. cenocepacia (29) [28]; P. fluorescens BIM B-582 (30) [63]; H. pylori STO2 (31) [29] ** ; K. pneumoniae O2a (32) [30] ** ; P. chloroaphis UCM B-106 (33) [64]; S. boydii type type 18 (34) [65]; S. enteritidis (35) [31]; S. paratyphi A (36) [32] ** ; S. enterica O41 (37) [33], O51 (38) [66], O60 (39) [67]; E. coli O43 (40) [68], O75 (41) [69], O115 (42) [34], O156 (43) [70]; A. doebereinerae type strain GSF71 T (44) [71], P. alcalifaciens O22 (45) [78], rhizobial and agrobacterial LPS inner core (46) [72]; and C. jejuni LOS core (47) [35] ** ; Bradyrhizobium sp. BTAi1 (48) [36] ** and P. cryohalolentis K5 T (49) [37].…”

Rhamnogalacturonan II: Chemical Synthesis of a Substructure Including α‐2,3‐Linked Kdo**

“…In particular, donor 21 represents the ideal glycosylation candidate as its COOBn functionality can be removed at a late stage of the synthesis during global deprotection and without any additional saponification steps. While glycosyl donors 15 [31] and 16 [32] were prepared according to published procedures, Kdo fluoride donor 21 was prepared in five steps from Kdo ammonium salt, previously obtained from d-arabinose and oxaloacetic acid following the Cornforth reaction. [33,34] Namely, Kdo ammonium salt 17 [34] was first converted into the corresponding carboxylic acid by stirring in water in the presence of Dowex H + resin (!18, 94 %), then the acid was treated with an ethereal solution of phenyldiazomethane, followed by the introduction of the 4,5-O-and 7,8-O-isopropylidene rings (!19, 48 % over two steps).…”