β-Glycosides of 2,3-Diazido-2,3-dideoxy-d-mannose, a Synthetic Precursor of a Rare Bacterial Cell-Wall Building Unit

Abstract

2,3-Diazido-2,3-dideoxy-beta-D-mannopyranoside derivatives were synthesized in order to prepare beta-glycosides of 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid, a rare moiety of bacterial oligosaccharides. A direct glycosyl donor, 4,6-di-O-acetyl-2,3-diazido-2,3-dideoxy-alpha-D-mannopyranosyl bromide, was prepared, and its synthetic capacity was tested in glycosylation reactions. An indirect route was also elaborated: 3-azido-3-deoxy-beta-D-glucopyranosides were converted into beta-D-mannopyranosides. The cis vicinal diazido function successfully tolerated the conditions of mild acidic hydrolysis, tritylation, Jones oxidation, TEMPO oxidation, acetolysis, and bromination with TiBr(4).

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

“…Spectroscopic data for the R-anomer: 1 H NMR (CDCl 3 , 400 MHz, HHÀCOSY, HSQC) δ 7.44À7.49 (m, 2H, CH arom ), 7.23À7.41 (m, 18H, CH arom ), 5.59 (s, 1H, CH Ph), 5.16 (s, 1H, H-1 0 ), 5.11 (d,1H,J = 11.4 Hz,CHH Bn),4.74 (d,1H,J = 12.1 Hz,CHH Bn),4.60À4.68 (m,3H,CHH Bn,CHH Bn,4.57 (d,1H, J = 12.0 Hz, CHH Bn), 4.52 (d, 1H, J = 11.9 Hz, CHH Bn), 4.05 (dd, 1H, J = 4.7, 10.3 Hz, H-6 0 ), 3.98À4.01 (m, 2H, H-3 0 , H-4 0 ), 3.94 (t, 1H, J = 9.1 Hz, H-3), 3.80À3.86 (m, 1H, H-5 0 ), 3.79 (t, 1H, J = 9.2 Hz, H-4), 3.63À3.74 (m, 4H, H-5, H-6, H-6, H-6 0 ), 3.53À3.58 (m, 2H, H-2, H-2 0 ), 3.39 (s, 3H, OMe); 13 C-APT NMR (CDCl 3 , 100 MHz, HSQC) δ 138.1, 137.7, 136.9 (C q ), 129.0, 128.9, 128. 8,128.7,128.5,128.3,128.2,128.1,128.0,127.6,127.0,125.8 (CH arom 4, 155.4, 151.3, 138.5, 137.8, 137.6, 137.4, 137.0, 136.5 (C q ), 129.2, 129.1, 129.0, 128.9, 128.8, 128.7, 128.6, 128.3, 128.1, 127.9, 126.3, 126.2, 126.0, 125.8, 125.3, 118.9, 118.7, 114.5, 114.4 1,166.8 (CdO Ac,CO 2 Me),138.6,138.3,138.0 (C q Bn),128.4,128.3,128.1,128.0,127.9,127.7,127.6 (CH arom ), 100.2 (C-1 0 ), 97.8 (C-1), 81.9 (C-3), 79.9 (C-2), 77.2 (C-4), 75.7, 74.5 (30). Donor 8β and acceptor 21 were condensed using the general protocol for Ph 2 SO/Tf 2 O-mediated glycosylations to yield disaccharide 30 (49%, R/β = 1:3.5).…”

“…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. of our study of 2,3-diazido-2,3-dideoxy mannopyranosyl 8 and mannopyranosyl uronate donors. 2,3-Diacetamido-dideoxy mannopyranosyl uronates are found in various bacterial capsular polysaccharides, 9 in which they are usually linked in a 1,2-cis fashion to the next sugar residue.…”

“…Work from our laboratory has revealed that condensations involving 2-azido-2-deoxy-4,6- O -benzylidene mannosyl donors proceed somewhat less β-selective than couplings with its C-2- O -benzyl counterpart . To further investigate the influence of different substitution patterns on glycosylation with mannosyl and mannuronic acid ester donors, we here report the results of our study of 2,3-diazido-2,3-dideoxy mannopyranosyl and mannopyranosyl uronate donors. 2,3-Diacetamido-dideoxy mannopyranosyl uronates are found in various bacterial capsular polysaccharides, in which they are usually linked in a 1,2- cis fashion to the next sugar residue.…”

Acceptor‐Reactivity‐Controlled Stereoconvergent Synthesis and Immunological Activity of a Unique Pentasaccharide from the Cell Wall Polysaccharide of Cutibacterium acnes C7

“…In particular, stereoselective approaches for the facile synthesis of β-linked-ManA2,3(NAc) 2 glycosides are rather scarce, which mainly rely on β-glucosylation using the neighboring-group participation effect of C-2 acyl group, followed by inversing the C-2-OH of glucose residue with azide reagent for nucleophilic substitution (S N 2) reaction and subsequent oxidation of C-6-OH to generate modified mannuronic acid unit bearing the 1,2-cis-glycosidic bond. [10] However, it becomes inefficient or very difficult for this method to synthesize oligosaccharides containing multiple these rare mannuronic acid residues. [11] To overcome the above challenges, we report here an efficiently stereocontrolled approach for the first total synthesis of the pentasaccharide 1 and its fragments 2-5 with an anomeric aminopentyl linker at the reducing end that can be used to conjugate with other biomolecules for future biological studies.…”