Synthesis of the Campylobacter jejuni 81‐176 Strain Capsular Polysaccharide Repeating Unit Reveals the Absolute Configuration of its O‐Methyl Phosphoramidate Motif

Abstract

The O-methyl phosphoramidate (MeOPN) motif is anon-stoichiometric modification of capsular polysaccharides (CPS) in % 70 %ofall Campylobacter jejuni strains.Infections by C. jejuni lead to food-borne illnesses and the CPS they produce are key virulence factors.T he MeOPN phosphorus atom in these CPS is stereogenic and is found as as ingle stereoisomer.However,todate,the absolute stereochemistry at this atom has been undefined. We report the synthesis of the three repeating units found in C. jejuni 81-176 CPS;o ne of these possesses aMeOPN group.Inthe course of these studies we established that the stereochemistry of the phosphorus atom in this MeOPN group is R. These studies represent the first unequivocal proof of stereochemistry of this group in any C. jejuni CPS.T he compounds produced are anticipated to be useful tools in investigations targeting the function and biosynthesis of this structurally-interesting modification, which so far has only been identified in campylobacter.

Biosynthetic Pathways to Nonproteinogenic α-Amino Acids

“…272,273 The timing of methylation and phosphoryl transfer reactions to ultimately transfer MeOPN to the CPS remain to be delineated, although synthetic routes have demonstrated that the phosphorus in MeOPN exhibits an R-configuration. 274…”

Total Syntheses of Conjugation-Ready Trisaccharide Repeating Units of Pseudomonas aeruginosa O11 and Staphylococcus aureus Type 5 Capsular Polysaccharide for Vaccine Development

“…Compound 34 is well poised for chain elongation to synthesize higher-order oligosaccharides and constitutes a protected repeating unit of S. aureus CP5. The conversion of azide to NHAc by using Zn/AcOH followed by treatment with Ac 2 O, MeOH, and Et 3 N, 56 purification on a silica gel column, and finally reductive removal of the remaining benzyl ethers and benzyloxycarbamate group by hydrogenolysis using H 2 (1 atm) and 20 wt % Pd(OH) 2 /C before passage through a Celite bed and lyophilization delivered target molecule 2 in 72% yield, over 3 steps. The 1 H NMR and 13 C NMR data of 2 correlated well with the earlier reported data.…”

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 CPS oligosaccharides and analogs obtained (Figure 2A) include those from Hib (1) [19]; S. pneumoniae (Sp) serotypes ST1 (2) [20] ** , ST2 (3) [10], ST3 (4)(5) [21] ** , ST5 (6) [46], ST8 (7a-7d) [12] ** , ST11A (8) [22], and ST12F (9) [47]; group B Streptococcus (GBS) or Streptococcus agalactiae types Ia (10) [23], II (11) [24], VII (12) [25]; carbapenem-resistant Klebsiella pneumoniae (CR-Kp) (13) [26]; A. baumannii K47 (14) [48]; S. aureus types 5 (15) [49,61] and strain M (16) [50]; B. mallei (17) [51,52]; C. jejuni RM1221 (18) [53] ** and 81-176 (19) [54]; Bacteroides fragilis CPS PS A1 RU (20) [55]; Morganella morganii (21) [56]; C. bolteae (22) [27] ** , K. kingae KK01 (23) [57], C. psychrerythraea 34H (24) [58] and S. typhi (25) [59]. Among these, compounds 2, 20, 21, and 45 are repeating units of zwitterionic polysaccharides (ZPSs).…”