Synthesis of Two Tetra‐ and Four Pentasaccharide Fragments of Shigella flexneri Serotypes 3a and X O‐Antigens from a Common Tetrasaccharide Intermediate

Abstract

Relying on trichloroacetimidate chemistry, six tetra-and pentasaccharide fragments of the {2)GlcpNAc-(1Ǟ} n ((E)AB Ac CD) n polymer were synthesized as their propyl glycosides by use of a common fully protected (E)AB Ac C intermediate (9). Tetrasaccharide 9 derived from the condensation of an EA donor and a B Ac C acceptor. Partial and full deprotection gave free tetrasaccharides (E)AB Ac C and (E)ABC, respectively. Alternatively, 9 was converted into a trichloroacetimidate donor, which provided linear pentasaccharides (E)AB Ac CD and (E)ABCD, following a reaction

Detailed Investigation of the Immunodominant Role of O‐Antigen Stoichiometric O‐Acetylation as Revealed by Chemical Synthesis, Immunochemistry, Solution Conformation and STD‐NMR Spectroscopy for Shigella flexneri 3a

“…In the present case, all data converge to suggest that the positioning of residue D within the saccharide chain impacts on the hydrodechlorination rate. Indeed, in accordance with the synthesis of Ac CD(E)A‐Pr, B Ac CD(E)A‐Pr ( 12 ), D(E)AB Ac C‐Pr, and B′ Ac CD(E)AB‐Pr, access to the octasaccharide 4 demonstrates that the Pd/C‐mediated hydrodechlorination of a N ‐trichloroacetyl group is faster when present at an end‐chain residue than when part of an intrachain residue. It was hypothesized that steric hindrance impaired the efficiency of the heterogenous conversion.…”

“…Alternatively, the acceptor 10 and the EA donor 7 were set to react in toluene containing catalytic trimethylsilyl trifluoromethanesulfonate (TMSOTf) (Scheme ). In contrast to the analogous B Ac C acceptor, which reacted smoothly with donor 7 at −78 °C, the larger acceptor B Ac CD(E)A ( 10 ) was poorly reactive. Incomplete glycosylation was observed when the reaction was carried out at −40 °C with up to 1.8 equivalents of the trichloroacetimidate 7 (Table , entries 1 and 2).…”

“…However, we showed previously that the reaction of a D(E)A trichloroacetimidate donor with a B acceptor led to a 1:1 mixture of the α and β condensation products D(αE)AB and D(βE)AB, respectively . Thus, capitalizing on our former work, we describe instead a stepwise synthetic route to the targets 1 and 2 from the pentasaccharide 6 and the building blocks 7 , 8 , and 9 (Figure ).…”

“…Likewise, an allyl aglycon was introduced as temporary anomeric protection of all intermediates. Moreover, as demonstrated decades ago and subsequently exploited in the synthesis of various bacterial oligosaccharides including SF3a, SF6, and SF1b O‐Ag substructures, the efficient Pd/C‐catalyzed hydrogenation of the allyl moiety into a propyl ether provided the targets as propyl glycosides. Furthermore, the 4 D ,6 D ‐diol was protected as an isopropylidene acetal, previously shown to avoid possible interference due to anisotropic shielding observed when using a benzylidene acetal in related contexts .…”

“…The 3 D ‐ O ‐levulinyl donor 8 was constructed in four high‐yielding steps from the known allyl glycoside 18 (Scheme ). Controlled base‐mediated transesterification of the fully protected 3‐ O ‐acetyl precursor 18 by using K 2 CO 3 in methanol provided the alcohol 19 (94 %), and the levulinyl group was installed [LevOH, N , N ′‐dicyclohexylcarbodiimide (DCC), 4‐dimethylaminopyridine (DMAP)] to furnish the intermediate 20 (98 %).…”