Synthesis of branched tri- to pentasaccharides representative of fragments of Shigella flexneri serotypes 3a and/or X O-antigens

Fragments of the {2)-[α-d-Glcp-(1→3)]-α-l-Rhap-(1→2)-α-l-Rhap-(1→3)-[Ac→2]-α-l-Rhap-(1→3)-β-d-GlcpNAc-(1→}_n ((E)AB_AcCD)_n polymer were synthesized. D(E)A, CD(E)A, _AcCD(E)A were obtained according to a linear strategy, whereas BCD(E)A and B_AcCD(E)A were derived from the condensation of appropriate BC and D(E)A building blocks. Oligosaccharides were synthesized as their propyl glycoside, relying on (i) the efficient trichloroacetimidate chemistry, (ii) a common EA allyl glycoside, and (iii) a 2-trichloroacetamido-d-glucopyranose precursor to residue D. Final Pd/C-mediated deprotection, run under a high pressure of hydrogen, ensured O-acetyl stability. All targets are parts of the O-antigen of Shigella flexneri 3a, a prevalent serotype. Non-O-acetylated oligosaccharides are shared by the S. flexneri serotype X O-antigen.     

Synthesis of oligosaccharides as potential novel food components and upscaled enzymatic reaction employing the β-galactosidase from bovine testes

The β-galactosidase from bovine testes (EC 3.2.1.23) promotes the transfer of a galactose unit to glucose or galactose-containing residues in manifold derivatives, establishing β1→3 linkages.The synthesis of several potentially biologically important oligosaccharides β-d-Galp-(1→3)-α-d-Glcp-(1→2)-β-d-Fruf2, β-d-Galp-(1→3)-β-d-Galp-(1→4)-α,β-d-Glcp4, β-d-Galp-(1→3)-α-d-Glcp-(1→4)-d-Glcp-ol/Manp-ol 6, β-d-Galp-(1→3)-α-d-Glcp-(1→6)-β-d-Fruf8, β-d-Galp-(1→3)-α-d-Glcp-(1→6)-[α-d-Glcp-(1↔2)]-β-d-Fruf10, α-d-Galp-(1→6)-[β-d-Galp-(1→3)]-α-d-Glcp-(1↔2)-β-d-Fruf12, β-d-Galp-(1→3)-α-d-Glcp-(1↔2)-β-d-Fruf-(1↔2)-β-d-Fruf14 has been reached in yields between 7 and 44% by implementation of this specific enzyme. In addition, we found that it is feasible to gain high yields without an enzyme-specific buffer and even making upscaled preparation on a gram scale.     

β-Mannosylation of N-acetyl glucosamine by propargyl mediated intramolecular aglycon delivery (IAD): synthesis of the N-glycan core pentasaccharide

An efficient and completely stereocontrolled synthesis of the N-glycan Manβ(1-4)GlcNAc disaccharide is achieved by propargyl mediated intramolecular aglycon delivery (IAD). Isomerisation of the 2-O-progargyl group of a manno thioglycoside to an allene is followed by iodonium ion mediated mixed acetal formation with the 4-OH of a protected GlcNAc derivative, and subsequent intramolecular glycosylation with complete control of anomeric stereochemistry. Access to this key disaccharide intermediate allows completion of the total synthesis of the core N-glycan pentasaccharide.     

Synthesis and characterization of novel vinyl copolymers containing N-vinylphthalimide: Comonomers reactivity ratios and thermal stability

N-Vinylphthalimide (NVPh) was copolymerized with p-methylstyrene (PMS), p-methoxystyrene (PMOS) and p-chlorostyrene (PClS) at 60 °C, with 2,2′-azo-bis-isobutyronitrile as an initiator. Copolymer composition was determined by elemental analysis in case of the N-vinylphthalimide and p-methylstyrene comonomer pair, whereas proton nuclear magnetic resonance was used for the analysis of the two other copolymers.The reactivity ratios for each comonomer pair were estimated by the classical Fineman-Ross and Kelen-Tüdõs linear techniques. These data showed that N-vinylphthalimide was less reactive in all the cases and that the comonomer distribution, that was basically random in the poly(N-vinylphthalimide-co-p-methylstyrene) and poly(N-vinylphthalimide-co-p-chlorostyrene) copolymers, was rather alternate in the third poly(N-vinylphthalimide-co-p-methoxystyrene) copolymer. The difference observed in the reactivity ratios was discussed in reference to the structure of the comonomer units and the parent radicals. The thermal properties of the copolymers and model homopolymers were investigated by differential scanning calorimetry and thermogravimetric analysis.     

An expeditious and efficient synthesis of β-d-galactopyranosyl-(1→3)-d-N-acetylglucosamine (lacto-N-biose) using a glycosynthase from Thermus thermophilus as a catalyst

Mutant glycosynthases or transglycosidases obtained from a Thermus thermophilus β-d-glycosidase (TtbGly) efficiently catalyzed the synthesis of β-(1→3)-disaccharides. Unfortunately, this regioselectivity was changed to the β-(1→4) one when N-acetylglucosamine derivatives were used as acceptors, thus precluding the possibility of synthesizing d-Galp-β-(1→3)-d-GlcpNAc (lacto-N-biose) or d-Glcp-β-(1→3)-d-GlcpNAc, which are useful synthons for the synthesis of antigen determinants. In contrast, we show in this work that, in the presence of phenyl 2-amino-1-thio-β-d-glucopyranoside, the ‘normal’ β-(1→3) regioselectivity of E338G TtbGly glycosynthase takes place. Thus, transglycosylations using α-galactosyl or α-glucosyl fluorides gave the corresponding phenyl β-d-glycopyranosyl-(1→3)-2-amino-2-deoxy-1-thio-β-d-glucopyranosides in high yields (88–97%). Subsequent selective N-acylation followed by NBS/water deprotection of the thiophenyl group afforded lacto-N-biose in high overall yields.     

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 and optical properties of conjugated N,N-dimethyl and thienyl end-capped 2,5-(arylethynyl)thiophene oligomer structures

End-capped (N,N-dimethylaminophenyl) and 2′-thienylethynyl 2,5-thiophene oligomer structures were synthesized by heterocoupling between the terminal acetylenes such as: p-(N,N-dimethylaminophenyl)ethyne (3) [or 1-(p-(N,N-dimethylaminophenyl)-2-p-(ethynylphenyl)ethyne, 4]; p-(β-ethenyl-2′-thienyl)phenylethyne (E-9) [or p-(β-ethynyl-2′-thienyl)phenylethyne, 11], and 2,5-diiodothiophene, catalyzed by the Cl₂Pd(PPh₃)₂/CuI system, in good to excellent yields. The 2,5-di[(3′,5′-di(trimethylsilylethynyl)phenyl]_x-1-ethynyl]thiophene oligomers were prepared by heterocoupling between 3′,5′-di[(trimethylsilylethynyl)phenyl]_x-1-ethyne (n = 0-2) terminal acetylenes and 2,5-diiodothiophene, in excellent yields. The terminal acetylenes were efficiently prepared by a specific protection-deprotection methodology. All the ethynylphenyl compounds obtained show fluorescence radiation emission, with a bathochromic shift of the wavelength that increases with the chain conjugation.     

Exploratory N-Protecting Group Manipulation for the Total Synthesis of Zwitterionic Shigella sonnei Oligosaccharides

Shigella sonnei surface polysaccharides are well-established protective antigens against this major cause of diarrhoeal disease. They also qualify as unique zwitterionic polysaccharides (ZPSs) featuring a disaccharide repeating unit made of two 1,2-trans linked rare aminodeoxy sugars, a 2-acetamido-2-deoxy-l -altruronic acid (l -AltpNAcA) and a 2-acetamido-4-amino-2,4,6-trideoxy-d -galactopyranose (AAT). Herein, the stereoselective synthesis of S. sonnei oligosaccharides comprising two, three and four repeating units is reported for the first time. Several sets of up to seven protecting groups were explored, shedding light on the singular conformational behavior of protected altrosamine and altruronic residues. A disaccharide building block equipped with three distinct N-protecting groups and featuring the uronate moiety already in place was designed to accomplish the iterative high yielding glycosylation at the axial 4-OH of the altruronate component and achieve the challenging full deprotection step. Key to the successful route was the use of a diacetyl strategy whereby the N-acetamido group of the l -AltpNAcA is masked in the form of an imide.     

Synthesis of poly(p-phenylene)s having alternating sugar and alkyl substituents by Suzuki coupling polymerization and evaluation of their main-chain conformations

This paper reports synthesis of poly(p-phenylene)s (PPPs) having alternating sugar and alkyl substituents by Suzuki coupling polymerization of a 1,4-dibromobenzene monomer having peracetylated glucose residues with a 1,4-benzene bis(boronic acid) having alkyl chains using Pd(PPh₃)₄ in a mixed solvent of THF and NaHCO₃ aq. at reflux temperature. The polymerization proceeded with the progress of frequent deacetylation, and thus, the crude product was acetylated, followed by the isolation procedures, giving the PPP having alternating peracetylated glucose and alkyl substituents. The structure of the isolated product was confirmed by the ¹H and ¹³C NMR measurements to be the desired PPP derivative. The M_n values were estimated by GPC analysis with DMF as the eluent to be 5400-12,700. The deacetylation of the polymer completely took place using sodium methoxide in methanol/THF. The conformation of the main-chain was evaluated by the CD spectrum in comparison with that of PPP only with the glucose substituents, indicating that the present PPP derivative had the flexible nature of the main-chain by introduction of the alkyl-substituted units between glucose-substituted units. The Suzuki coupling of a 1,4-dibromobenzne monomer having disaccharide substituents with the benzene bis(boronic acid) monomer was also performed under the similar conditions. The product was precipitated from the reaction mixture, which was simply isolated by filtration. The isolated polymer was purified further by reprecipitation into diethyl ether and its structure was a PPP having free disaccharide or monosaccharide residues. This indicated occurrence of complete deacetylation as well as partial degradation of the glycosidic linkages in the disaccharides during the polymerization. The main-chain of the obtained polymer had also the flexible nature. The fluorescence spectra of the obtained PPP derivatives in this study were also measured.     

DFT study of the reaction sites of N,N′-substituted p-phenylenediamine antioxidants

The geometry of N,N′-diphenyl-p-phenylenediamine (DPPD), N-phenyl-N′-(1′-methylbenzyl)-p-phenylenediamine (SPPD), N-phenyl-N′-(1,3-dimethyl-butyl)-p-phenylenediamine (6PPD), N-phenyl-N′-isopropyl-p-phenylenediamine (IPPD), and N-(1-methyl-1-phenylethyl)-N′-phenyl-p-phenylenediamine (CPPD) as well as of their dehydrogenation products has been optimized at B3LYP/6-31G^∗ level of theory. Our results support the idea of formation of stable ketimine Ph-NC structures (instead of quinonediimine structures) during consecutive dehydrogenation of SPPD, 6PPD, and IPPD antioxidants despite the formation of tertiary carbon-centered radicals in the first dehydrogenation step is energetically preferred for SPPD only.     

Synthesis of N,N-diethyldithiocarbamate functionalized 1,4-polyisoprene, from natural rubber and synthetic 1,4-polyisoprene

N,N-Diethyldithiocarbamate functionnalized 1,4-polyisoprenes were prepared from 1,4-polyisoprenes (natural or synthetic). The syntheses were performed by nucleophilic addition of N,N-diethyldithiocarbamate salts upon oxirane rings of epoxidized units according to a SN2 mechanism with ring opening. Studies on model molecules of epoxidized 1,4-polyisoprene units (1,2-epoxy-1-methylcyclohexane and 4,5-epoxy-4-methyloctane) were previously achieved to develop the procedure. The best yields were obtained at low temperature in polar medium, and more especially in water with sodium N,N-diethyldithiocarbamate (DEDT-Na) as reagent. A diastereospecific addition was noted when reaction was performed in water with DEDT-Na. Afterwards, the developed procedure was successfully generalized to epoxidized synthetic polyisoprenes and epoxidized natural rubber (in THF, then in latex medium). Excellent results were obtained in latex medium with epoxidized natural rubber (ENR) latices. As with the models, a diastereospecific addition of sodium N,N-diethyldithiocarbamate trihydrate onto epoxidized 1,4-polyisoprene units of ENR was observed at the condition to bring the latex medium to pH 8 before introduction of DEDT-Na. Influence of temperature, drc, and DEDT-Na concentration were successively examined to determine the best conditions of the addition on ENR latices.     

Synthesis of N,N-dialkylaminobenzonitriles and halo-(N,N-dialkyl)benzamidines by reaction of halobenzonitriles with lithium amides

3- and 4-N,N-Dialkylaminobenzonitriles and 4-chloro-(N,N-dialkyl)benzamidines were isolated by reacting 4-chlorobenzonitrile with hindered lithium amides under thermodynamic (0 °C) and kinetic control conditions (−78 °C), respectively. As previously reported, a benzyne mechanism seems to be confirmed since N,N-dialkylaminobenzonitriles are formed. Only benzamidines were isolated in fair to high yields at both 0 °C and −78 °C with non-hindered lithium amides. Exploitation and mechanistic rationale of the reaction of different halobenzonitriles are also reported.     

Photolabile thymidine cleavable with a 532 nanometer laser

The synthesis and characterization of a novel 3′ p-hydroxyphenacyl-caged thymidine bearing a 5′ N,N-diisopropylcyanoethylphosphoramidite is presented representing a new methodology for the photoregulation of PCR and gene expression. Solid phase oligonucleotide synthesis affords a primer blocked at the 3′ position, which could function as a phototrigger for polymerase activity. The caging group exhibits quantitative photolysis in 15 s using a 532 nm green hand laser.     

Synthesis of enantiopure (S)-7-hydroxy-3-amino-3,4-dihydro-2H-1-benzopyran en route to (+)-scyphostatin

(S)-7-Hydroxy-3-amino-3,4-dihydro-2H-1-benzopyran, a key synthetic intermediate towards the total synthesis of (+)-scyphostatin, has been prepared in >98% ee. Key synthetic steps were (i) the oxidative dearomatization of an l-tyrosine derived phenol, (ii) the transformation of the resulting p-quinol acetate to the corresponding resorcinol upon exposure to Thiele reaction conditions and, (iii) the direct formation of the benzopyran ring upon treatment of an N-Boc protected 4-(2-acetoxybenzyl)oxazolidin-2-one with sodium methoxide.     

Synthetic application of in situ generation of N-acyliminium ions from α-amido p-tolylsulfones for the synthesis of α-amino nitriles

In the presence of catalytic amount of bismuth bromide (5 mol %) the α-amido p-tolylsulfones are converted into N-acyliminium ions, which undergo the nucleophilic addition of trimethylsilyl cyanide (TMSCN) to provide the N-protected α-amino nitriles in very good yield. A variety of α-amido p-tolylsulfones were prepared from aromatic as well as aliphatic aldehydes for the synthesis of α-amino nitriles.     

Synthesis of zwitterionic 4-hydroxy-2(1H)-quinolinone derivatives

Zwitterionic 4-hydroxy-2(1H)-quinolinone derivatives were synthesized through a unique reaction of 4-hydroxy-2(1H)-quinolinone with p-benzoquinone and N-heterocyclic aromatics. The zwitterions possessed astropisomeric nature. A possible mechanism of the reaction was presented.     

Synthesis of cyclic peptides via O-N-acyl migration

We describe here a novel and convenient synthesis of head-to-tail cyclic peptide avoiding racemization. Linear depsipeptides including a serine residue as the key element for ester bond formation and acyl transfer were synthesized on 2-chlorotrityl chloride resin. After cleavage from the resin, intramolecular head-to-tail cyclization was performed in solution by C-terminal activation of urethane protected O-acyl serine residue. After removal of the N^α-serine protecting group, the final step consisted in O-N-acyl migration reaction on the ‘switch’ or ‘click’ element to restore native cyclic peptides.     

Synthesis of meso-tetraphenyl porphyrins via condensation of dipyrromethanes with N-tosyl imines

A new synthetic route for the synthesis of 5,10,15,20-tetraphenyl porphyrins has been developed based on the reaction of 5-substituted dipyrromethanes with N-tosyl imines in the presence of a metal triflate catalyst. meso-Substituted tetraphenyl porphyrins were synthesized in a two-step process. The first step of the method is the metal triflate-catalyzed condensation of 5-substituted dipyrromethanes with N-tosyl imines to form a porphyrinogen intermediate and the second step is the oxidation of the porphyrinogen to porphyrin. The method was applied to the synthesis of trans-A₂B₂-tetraarylporphyrins and the products were obtained with only a trace amount of one scrambling product. The synthesis of two important building blocks for porphyrin synthesis, mono and di-sulfonamide alkylated 5-substituted dipyrromethanes, was achieved by the addition of 5-substituted dipyrromethane to N-tosyl imine. The application of mono and di-sulfonamide alkylated 5-substituted dipyrromethanes in ‘2+2’ porphyrin formation reactions is presented.     

Synthesis of photolabile o-nitroveratryloxycarbonyl (NVOC) protected peptide nucleic acid monomers

The chemical synthesis of peptide nucleic acid (PNA) monomers was accomplished using various combinations of the o-nitroveratryloxycarbonyl (NVOC) group (N-aminoethylglycine backbone) and base labile acyl-type nucleobase protecting groups (anisoyl for adenine and cytosine; isobutyryl for guanine), thus offering a photolithographic solid-phase PNA synthetic strategy compatible with photolithographic oligonucleotide synthesis conditions and allowing the in situ synthesis of PNA microarrays in an essentially neutral medium, by avoiding the use of the commonly used deprotection reagents such as trifluoroacetic acid or piperidine. Convenient methods were also explored to prepare 1-(carboxymethyl)-4-N-(4-methoxybenzoyl)cytosine and 9-(carboxymethyl)-2-N-(isobutyryl)guanine with good yields.     

An efficient synthesis of a hexasaccharide—the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar A

A general method for the synthesis of 2-xylose or glucuronic acid branched (1→3)-linked mannose oligosaccharides has been developed. As a typical example, the synthesis of the methyl glycoside of β-d-GlcpA-(1→2)-α-d-Manp-(1→3)-[β-d-Xylp-(1→2)-]α-d-Manp-(1→3)-[β-d-Xylp-(1→2)-]α-d-Manp, the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar A, was achieved in a regio- and stereoselective manner.