Concise synthesis of a pentasaccharide repeating unit corresponding to the O-antigen of Escherichia coli O102

An efficient synthetic strategy has been developed for the synthesis of a pentasaccharide repeating unit of the O-antigen of Escherichia coli O102 strain. The target pentasaccharide 1 has been synthesized using a [2+3] block glycosylation strategy. All glycosylation steps are highly stereoselective and high yielding. Concept of armed-disarmed and orthogonal glycosylation strategies has been applied during the synthesis. The target compound has been synthesized using the minimum number of steps.     

Synthetic directions towards capsular polysaccharide of Streptococcus pneumoniae serotype 18C

An efficient synthetic strategy has been developed for the synthesis of the tri, tetrasaccharide block and pentasaccharide corresponding to the capsular polysaccharide of Streptococcus pneumonia serotype 18C as their 2-aminoethyl glycosides. A one-pot glycosylation-deprotection, sequential glycosylations strategy has been adopted for the construction of the fragments and pentasaccharide derivative, which were then transformed into target compound after a series of functional group transformations. The synthetic method relies on the use of p-methoxybenzyl ether as an in situ-removable protecting group to reduce the number of reaction steps significantly. Here H₂SO₄-silica has been used successfully as a promoter for all glycosylation reaction. In addition, the synthetic target also contained a free amino group at its reducing end, facilitating its conjugation with other molecules for various biological studies and applications.     

Convergent synthesis of a common pentasaccharide-repeating unit corresponding to the O-specific polysaccharide of Escherichia coli O4:K3, O4:K6, and O4:K12

A convergent chemical synthesis of a pentasaccharide found in the O-specific polysaccharide of Escherichia coli O4:K3, O4:K6, and O4:K12 has been achieved in excellent yield. A [3+2] block synthetic strategy has been adopted to couple a disaccharide donor 11 with a trisaccharide acceptor 10 for the construction of the pentasaccharide derivative 12 which on deprotection furnished target pentasaccharide 1 as its 4-methoxyphenyl glycoside. Disaccharide thioglycoside donor 11 and trisaccharide acceptor 10 were prepared from suitably protected monosaccharide intermediates. Yields were excellent in all steps.     

Convergent synthesis of a pentasaccharide repeating unit corresponding to the cell wall O-antigen of Salmonella enterica O44

A convergent synthetic strategy has been developed for the synthesis of a pentasaccharide fragment corresponding to the O-antigen of Salmonella enterica O44 strain. An intermediate tetrasaccharide derivative was prepared by a [2+2] block glycosylation of two disaccharide derivatives. The p-methoxybenzyl (PMB) group has been used as the in situ temporary protecting group minimizing the number of functional group manipulation steps. The application of the armed–disarmed glycosylation concept reduced the number of steps in the synthetic strategy. The glycosylation steps were highly stereoselective and high yielding.     

Straightforward sequential and one-pot synthesis of a pentasaccharide repeating unit corresponding to the cell wall O-antigen of Shigella boydii type 18

Synthesis of a pentasaccharide repeating unit corresponding to the cell of wall O-antigen Shigella boydii type 18 has been achieved by sequential as well as iterative glycosylations in one-pot. Use of p-methoxybenzyl group (PMB) as an in situ removable protecting group allowed obtaining the desired pentasaccharide derivative in a generalized glycosylation condition and in one-pot condition. Synthesis of a beta-L-rhamnosidic linkage present in the molecule has been successfully achieved using l-rhamnosyl thioglycoside donor having a picoloyl group at remote C-3 position influencing beta selectivity in the glycosylation. A combination of N-iodosuccinimide (NIS) and perchloric acid supported over silica (HClO₄–SiO₂) has been used as thiophilic glycosylation promoter in all glycosylation reactions. TEMPO mediated selective oxidation of the primary hydroxyl group has been carried out at the late stage of the synthetic strategy.     

Expedient synthesis of a tetrasaccharide and a pentasaccharide corresponding to the cell wall O-antigen of Escherichia coli O77 and Escherichia coli O17

A concise chemical synthetic strategy has been developed for the synthesis of a tetrasaccharide and a pentasaccharide corresponding to the O-antigen of Escherichia coli O77 and E. coli O17 strains, respectively using [2+2] and [3+2] block glycosylation approaches from suitably functionalized common monosaccharide intermediates. All of the intermediate steps are high yielding while the glycosylation steps are highly stereoselective. A number of recently developed methodologies have been used in the synthesis.     

Facile synthesis of a pentasaccharide repeating unit corresponding to the common O-antigen of Salmonella enterica O57 and Escherichia coli O51

A concise chemical synthetic strategy has been developed for the synthesis of a pentasaccharide present in the O-antigen of Salmonella enterica O57 and Escherichia coli O51 strains. A sequential glycosylation strategy has been adopted for the synthesis of the target pentasaccharide. All intermediate steps are high yielding and the glycosylation steps are stereoselective. A number of recently developed methodologies have been used in the synthesis.     

Synthesis of penta- and hexasaccharide fragments corresponding to the O-antigen of Escherichia coli O150

The chemical synthesis of a pentasaccharide and a hexasaccharide corresponding to the O-antigen of Escherichia coli O150 has been achieved using sequential glycosylation and [3+3] block glycosylation strategies. Suitably protected monosaccharide synthons have been prepared from the commercially available reducing sugars and then stereoselectively coupled to give the pentasaccharide and a hexasaccharide in excellent yields. 4-Methoxyphenyl and 2-(4-methoxyphenoxy) ethyl groups have been used as the anomeric-protecting groups in the target pentasaccharide and a hexasaccharide, respectively.     

Synthetic directions of acidic hexasaccharide repeating unit of the O-antigen of Cronobacter sakazakii HPB 2855 using one pot glycosylation

Synthesis of a hexasaccharide repeating unit of the O-antigen of Cronobacter sakazakii HPB 2855 has been achieved by sequential glycosylations and one-pot glycosylation-deprotection techniques. The synthetic method relies on the use of a p-methoxybenzyl ether as an in situ-removable protecting group to reduce the number of reaction steps significantly. All the glycosylations have been accomplished by the activation of the only one class of simple and stable thioglycosyl donors using NIS in the presence of sulfuric acid immobilized on silica (H₂SO₄-silica) as a Brönsted acid catalyst to work as a promoter. The stereo outcomes of all the glycosylation steps were excellent with satisfactory yield. TEMPO mediated selective oxidation of the primary hydroxyl group has been carried out at the late stage of the synthetic strategy to achieve the required uronic acid motif.     

Synthesis of a pentasaccharide repeating unit of the O-antigen of enteroadherent Escherichia coli O154 strain

A straightforward linear synthetic strategy has been developed for the synthesis of the pentasaccharide repeating unit of the cell wall O-antigenic polysaccharide of enteroadherent Escherichia coli O154 strain. Newly developed glycosylation conditions using glycosyl trichloroacetimidate derivatives as glycosyl donors and nitrosyl tetrafluoroborate as the glycosylation activator have been used in all of the glycosylation reactions throughout the synthetic scheme. The stereochemical outcomes of the glycosylations were excellent and the yields were very good.     

Total synthesis of the aminopropyl functionalized ganglioside GM1

GM1 is a common ganglioside pentasaccharide present on mammalian cell surface.It has been shown to play important roles in cellular communications and initiation of β-amyloid aggregation.In order to synthesize GM1,an efficient synthetic route was developed via a [3+2] strategy.The GM3 trisaccharide acceptor bearing an azido propyl group at the reducing end was prepared using the traditional acetamide protected sialyl thioglycosyl donor,which gave better stereoselectivity than sialyl donors protected with trichloroacetamide or oxazolidinone.The glycosylation of the axial 4-hydroxyl group of GM3 by the disaccharide donor was found to be highly dependent on donor protective groups.Donor bearing the more rigid benzylidene group gave low glycosylation yield.Replacing the benzylidene with acetates led to productive coupling and formation of the fully protected GM1 pentasaccharide.Deprotection of the pentasaccharide produced GM1 functionalized with the aminopropyl side chain,which will be a valuable probe for biological studies.     

Synthesis of a Pentasaccharide Repeating Unit of the Extracellular Polysaccharide Produced by Lactobacillus Delbrueckii Subsp. Bulgaricus 291

A pentasaccharide methyl glycoside has been synthesized efficiently using a modified glycosylation strategy. This pentasaccharide is a repeating unit of the exopolysaccharides produced by Lactobacillus delbrueckii subsp. bulgaricus 291.     

Synthesis of tri- and pentasaccharide fragments corresponding to the O-antigen of Shigella boydii type 6

A convenient synthetic strategy for the synthesis of the acidic pentasaccharide repeating unit and its trisaccharide fragment corresponding to the O-antigen of Shigella boydii type 6 has been successfully developed. A stereoselective sequential glycosylation method has been exploited to obtain the target tri- and pentasaccharide derivatives. Most of the synthetic intermediates were solid and prepared in high yields from commercially available reducing sugars following a series of protection–deprotection reactions. A late-stage TEMPO mediated selective oxidation reaction finally resulted in the pentasaccharide containing a glucuronic acid unit. A 2-(4-methoxyphenoxy) ethyl group has been chosen as the anomeric protecting group to provide trisaccharide and pentasaccharide derivatives linked to an ethylene glycol linker.     

Synthesis of an antimetastatic tetrasaccharide β-D-Gal-(1→4)-β-d-GlcpNAc-(1→6)-α-D-Manp-(1→6)-β-D-Manp-OMe

An antimetastatic tetrasaccharide T₁,β-D-Gal-（1→4）-β-D-GlcpNAc-（1→6）-α-D-Manp-（1→6）-β-D-Manp-OMe,was synthesized with two approaches.The first approach was a conventional method employing thioglycoside and Koenigs-Knorr glycosylation reaction in 24%overall yield.The second one was a novel route through the azidoiodo-glycosylation strategy by using 2-iodo-2-deoxylactosyl azide as the donor in 36%overall yield.     

First synthesis of a pentasaccharide repeating unit of the O-antigenic polysaccharide from enterohaemorrhagic Escherichia coli O48:H21

A concise synthesis of a pentasaccharide as its 4-methoxyphenyl glycoside, found in the O-antigenic polysaccharide of enterohaemorrhagic Escherichia coli O48:H21 has been achieved for the first time in excellent yield. Most of the intermediate steps are high yielding and the stereooutcome of each glycosylation step was excellent. Stereoselective glycosylation and removal of the 4-methoxybenzyl group were achieved in one-pot by tuning the reaction conditions. A late-stage TEMPO-mediated oxidation strategy has been adopted for the oxidation of a primary hydroxyl group to carboxylic acid.     

Reactions of β-substituted amines-IV: Kinetics and stereochemistry of the thermal to (r) 3-chloro-1-ethylpiperidine,and the stereo-chemical course of their reactions with nucleophiles

The rate of the thermal rearrangement of (S) 2 chloromethyl-1-ethylpyrrolidine [(S)-1a] to (R)-3-chloro-1-ethylpiperidine [(R) 2a] has been examined at three temperatures in benzene by PMR and polarimetry. The rearrangement was shown to be completely stereospecific and to obey a simple first order rate law. The calculated E_a ΔH3 and ΔS3 were 22 ± 2 $\text{kcal}\text{mole}$ (25°), 21 ± 2.5 $\text{kcal}\text{mole}$ (25°) and - 10 ± 2 e.u. (0°K) respectively. The effect of solvents having differing dielectric constants was also studied. A transition state 9'a and an ion pair intermediate 3a are suggested for the rearrangement. The stereochemical course of the reactions of (S)-1a, (R)-2a and (S)-2a with hydroxide and methoxide ions have been shown to be 100% stereospecific with an uncertainty of about 1%. The absolute configurations of all optically active reactants and products [(S)- and (R)-4a, (S)-4b (R)- and (S)-5a, (R)-5b, (S,S')-6a, (S,R')-7a and (R,R')-8a] were established by chemical correlations with known compounds or by ORD and chemical inference. The ring opening of both the primary and secondary aziridinium ion positions of 1-azonia-1-ethylbicyclo [3.1.0]hexane [(S)-3a] by nucleophiles proceeds entirely by S_N2 processes. The conversion of (R)-1-ethyl-3-hydroxypiperidine [(R)-5a] to (S)-2a. HCl with thionyl chloride in chloroform proceeds by inversion with 4.8% racemization, whereas the thermal rearrangement of (S)-1a to (R)-2a occurs with complete retention of absolute configuration.     

Synthesis of the pentasaccharide repeating unit of the O-antigen of Escherichia coli O175 using one-pot glycosylations and its conformational analysis

Synthesis of a pentasaccharide repeating unit of the cell wall O-antigenic polysaccharide of enteroaggregative Escherichia coli O175 has been achieved using one-pot, three components [1+2+2] block glycosylations. The intermediate steps were good yielding and satisfactory stereoselectivity was observed in the glycosylations. The synthesized pentasaccharide was subjected to conformational analysis in aqueous environment using 2D ROESY NMR spectral analysis in conjugation with molecular dynamics (MD) simulation technique.     

Enkephalin-based drug design: conformational analysis of O-linked glycopeptides by NMR and molecular modeling

Glycosylation provides an effective means of enhancing penetration of the blood–brain barrier by pharmacologically active peptides. Glycosylated enkephalin analogues demonstrate much greater analgesic effects than their unglycosylated counterparts when administered peripherally. The solution conformations of glycopeptide enkephalin analogues with the sequences H-Tyr-c-[d-Cys-Gly-Phe-d-Cys]-Ser(β-O-Glcp)-Gly-NH₂, 2, and H-Tyr-c-[d-Cys-Gly-Phe-d-Cys]-Ser(α-O-Glcp)-Gly-NH₂, 3, have been determined by NMR and molecular modeling, and were compared to the unglycosylated peptide H-Tyr-c-[d-Cys-Gly-Phe-d-Cys]-Ser-Gly-NH₂, 1, to determine the impact of glycosylation on peptide conformation. The only observed conformational effects were on the residue of attachment, Ser⁶, and on the adjacent Gly⁷-amide. This has important implications in peptide-based drug design in that strategically placed glycosylation can improve transport without destruction of the receptor selectivity of a pre-existing non-glycosylated peptide pharmacophore.     

Synthesis of a new glycosphingolipid from the marine ascidian Microcosmus sulcatus using a one-pot glycosylation strategy

A novel neutral glycosphingolipid found in Microcosmus sulcatus containing a β-d-Galp(1→4)[α-d-Fucp-(1→3)]β-d-Glcp-(1→)Cer motif was synthesized. Trisaccharide derivatives were synthesized using trimethylsilyltrifluoromethanesulfanate (TMSOTf) and N-iodosuccimide (NIS)/trifluoromethane sulfonic acid (TfOH) as the promoters. Synthesis was achieved with an efficient one-pot glycosylation strategy. This is the first report of a one-pot glycosylation strategy using the procedure of Boons et al. for the synthesis of a natural product. Coupling of trisaccharide derivative 19 and ceramide derivative 20 by TMSOTf afforded the glycosphingolipid derivative 21. The fully protected glycoside was deprotected to give the target glycosphingolipid 2.     

Synthesis of monohydridohexamethylbenzeneruthenium(II) complexes containing group V donor ligands. Isomerism arising from cyclometallation of a tertiary phosphine at aliphatic and aromatic carbon atoms

The η-hexamethylbenzenehydridoruthenium(II) complexes RuHCl(η-C₆Me₆)L (L = PPh₃ (11), AsPh₃ (12), P(C₆H₄-p-F)₃ (14), P(C₆H₄-p-Me)₃ (15), P(C₆H₄-p-OMe)₃ (16), P-t-BuPh₂ (17), P-i-PrPh₂ (18), P-i-Pr₃ (19), PCy₃ (20) and P-t-BuMe₂ (21)) have been made by heating [RuCl₂(η-C₆Me₆)]₂, the ligand and sodium carbonate in propan-2-ol. The triarylphosphine complexes 11, 14 and 15 react with methyllithium to give aryl ortho-metallated hydridoruthenium(II) complexes such as $\text{RuH(}\text{o}\text{-C}{}_6\text{H}{}_4\text{P}$Ph₂)(η-C₆Me₆) (22) and 19 similarly gives the isopropyl cyclometallated complex $\text{RuH(CH}{}_2\text{CHMeP}$-i-Pr₂(η-C₆Me₆) (29) as a mixture of diastereomers. Reaction of 17 with methyllithium gives initially the t-butyl cyclometallated complex $\text{RuH(CH}{}_2\text{CMe}{}_2\text{P}$Ph₂)(η-C₆Me₆) (25) which isomerizes by a first order process (k$\text{0}\text{?}$.2 h^?1 in C₆D₆ or THF-d₈ at 50°C) to the aryl ortho-metallated complex $\text{RuH(}\text{o}\text{-C}{}_6\text{H}{}_4\text{P}$-t-BuPh)(η-C₆Me₆) (26). The similarly generated isopropyl cyclometallated complex $\text{RuH(CH}{}_2\text{CHMeP}$Ph₂)(η-C₆Me₆) (27) has not been isolated in a pure state owing to rapid isomerization to $\text{RuH(}\text{o}\text{-C}{}_6\text{H}{}_4\text{P}$-i-PrPh)(η-C₆Me₆) (28); both 27 and 28 exist as a pair of diastereomers. The formation of the cyclometallated complexes and the isomerizations are thought to involve intermediate 16-electron ruthenium(O) complexes Ru(η-C₆Me₆)L.