Stereoselective Synthesis of 2,3-Diamino-2,3-dideoxy-β-d-mannopyranosyl Uronates

Abstract

With the aim to find an efficient synthetic procedure for the construction of 2,3-diamino-2,3-dideoxy-β-D-mannuronic acids, we evaluated three mannosyl donors: (S)-phenyl 4,6-di-O-acetyl-2,3-diazido mannopyranoside, (S)-phenyl 2,3-diazido-4,6-O-benzylidene mannopyranoside, and (S)-phenyl 2,3-diazido mannopyranosyl methyl uronate. The first two mannosylating agents are rather unselective or slightly α-selective in their condensation with three different acceptors. The mannuronic acid donor on the other hand reliably provides the desired β-mannosidic linkage. A mechanistic rationale is put forward to account for the different behavior of the three donor types. Suitably protected 2,3-diazido mannuronic acids were employed to construct the all-cis-linked tetrasaccharide repeating unit of the capsular polysaccharide of Bacillus stearothermophilus , featuring two 2,3-diacetamido-2,3-dideoxy-β-D-mannuronic acids.

Automated fluorous-assisted solution-phase synthesis of β-1,2-, 1,3-, and 1,6-mannan oligomers

“…10 The oxidation of the primary alcohol by 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO) and (diacetoxyiodo)benzene (BAIB) generated the uronic acid 3 . 6a Esterification of the carboxylic acid with methyl iodide (MeI)/K 2 CO 3 gave the fully protected methyl mannuronate 4 . 6a N -Bromosuccinimide (NBS) removed the anomeric thiophenyl group to produce hemiacetal 5 with a free anomeric hydroxyl group.…”

“…4a,b Previously we have demonstrated the automated solution-phase synthesis 5a of a β -1,4-mannan hexamer 5b and an insect N -glycan structure 5c by applying a β -directing C-5 carboxylate (mannuronate) methodology inspired in part by van der Marel and coworkers. 6 Unlike the more common 4,6- O -benzylidene-acetal technique for β -mannoside formation invented by Crich and coworkers 7 , the mannuronate glycosyl donor allows a more straightforward deprotection strategy, higher glycosylation temperature, and robustness against acidic conditions. 6 However, the generality of this approach to making other β -mannoside oligomers such as the β -1,2-, 1,3- and 1,6-mannans was unclear.…”

“…6 Unlike the more common 4,6- O -benzylidene-acetal technique for β -mannoside formation invented by Crich and coworkers 7 , the mannuronate glycosyl donor allows a more straightforward deprotection strategy, higher glycosylation temperature, and robustness against acidic conditions. 6 However, the generality of this approach to making other β -mannoside oligomers such as the β -1,2-, 1,3- and 1,6-mannans was unclear. 8 Herein we report a series of mannuronate building blocks to test their utility in automated solution-phase syntheses for the production of β -1,2-, 1,3- and 1,6-mannans.…”

Mannuronic Acids: Reactivity and Selectivity

“…3). [31] Because the glycosylation behavior of 2,3-diazido mannosylating agents has been rarely investigated, [32] we also examined S-phenyl 2,3-diazido-4,6-Obenzylidene mannopyranoside 54 and S-phenyl 4,6-di-O-acetyl-2,3-diazido mannopyranoside 55 as potential donors for the construction of the β-2,3-diaminomannosyl bond. Variable temperature NMR experiments revealed that all three donors were rapidly transformed into their α-anomeric triflates upon treatment with Ph 2 SO/Tf 2 O at -80 • C, as depicted in Figure 3.…”

“…The β-selectivity of the diazidomannuronate donor was exploited in the assembly of a tetrasaccharide 73, [31] representing the [→4)-β-D-ManpA2,3(NAc) 2 -(1→6)-α-DGlcp-(1→4)-β-D-ManpA2,3(NAc) 2 -(1→3)-α-D-GlcpNAc-(1→] repeating unit of the secondary cell wall polysaccharide of Bacillus stearothermophilus (Sch. 5).…”