Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• for the high selectivity observed in the formation of compound 6 and, consequently, for the attainment of the pure α-H-phosphonate 7. Indeed, the desilylation of the 2-azido counterpart of intermediate 5 provided a mixture of anomers. On the other hand, the same reaction carried out on a 2-acetamido

• equilibration of the anomers occurs during this reaction. We, therefore, ascribed the high stereoselectivity observed in the formation of compound 7 to the stability of compound 6, whose configuration is preserved during the reaction with salicylchlorophosphite. This finding introduced a great improvement in

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• aq NaHCO3 (200 mL) and brine (200 mL). The organic layer was dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by FC (silica, petroleum ether/ethyl acetate 10:1) to afford Ac4GlcNCyoc (1) as a mixture of anomers (1.08 g, 2.36 mmol, 26%). Rf = 0.36

• (petroleum ether/ethyl acetate 1:1); HRMS m/z: [M + Na]+ calcd for C20H27NO11, 480.14763; found, 480.14511. Further purification by semi-preparative HPLC (45% A for 10 min, then 45–70% A for 15 min) allowed separation of the anomers. Retention time β-anomer: 15 min, α-anomer: 17.2 min. α-Anomer: 1H NMR (400

• /ethyl acetate 1:1 –> 1:2) to afford Ac4GalNCyoc (2) as a mixture of anomers (551 mg, 1.2 mmol, 15%). Rf = 0.33 (petroleum ether/ethyl acetate 1:1); HRMS m/z: [M + Na]+ calcd for C20H27NO11, 480.14763; found, 480.14551. Further purification by HPLC (45% A for 10 min, then 45–70% A for 15 min) allowed

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• . Results and Discussion The syntheses of 5 and 6 (Scheme 1) generally followed a ring closing metathesis (RCM) strategy that had been established previously [9]. C4,C6-O-Benzylidene-protected allyl glucoside 7, as a mixture of α- and β-anomers, was the starting material for the synthesis. In the first step

• , the C2 and C3 hydroxy groups were converted to methyl ethers via alkylation with iodomethane in the presence of sodium hydride to give compounds 8a and 8b (3:1, 66% combined yield). At this point the α- and β-anomers could be separated by column chromatography. Each anomer was then carried through the

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• was also tested by ITC and a Kd of 50 μM was obtained, which is significantly higher than the Kd for α-MeFuc (0.43 μM) [41] (data not shown). This confirms that lecB has lower affinity for β-fucosides than for the α-anomers, but the trimeric β-fucoside cluster 14 still demonstrated reasonable binding

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• use of compound 6 as nucleobase acceptor improved the yield of nucleosides 7α,β in general and led to an acceptable β:α = 2.5:1 ratio of anomers. Subsequent saponification of 7α,β (unseparable by flash chromatography) proved to be tricky and after testing a series of standard techniques, only

• treatment with Bu4NOH in a mixed organic/aqueous solvent gave nucleosides 8α,β in good yield. It was at this step where the two anomers could be readily separated by flash chromatography. Continuing with 8β the synthesis of 10 was concluded by standard tritylation (→ 9) and phosphitylation. To extend on the

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• a mixture of anomers (α:β = 2:3, 93% for two steps). Then, the other two hydroxy groups were protected as 2,4-dichlorobenzyl ether. Compound 8 was isolated in 95% yield after reacting compound 7 with NaH and 2,4-dichlorobenzyl chloride in anhydrous DMF. 2,4-Dichlorobenzyl chloride was used because

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• synthesize the triazole-containing lactosylcalixarenes 3 and 4. We first attempted to prepare the lactoside derivative 14 by reacting peracetylated-lactose with 2-(2-(2-chloroethoxy)ethoxy)ethanol in the presence of BF3·Et2O [45]. However, we could only obtain a mixture of α and β-anomers (α/β ratio 2:3

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• -di-O-(tri-isopropylsilyl)-α-D-arabinofuranosyl chloride, the condensation of which with 2,6-dichloropurine gave an 1:3.5 α/β mixture of the relevant nucleosides. This mixture was treated with ammonia to replace the C-6 chlorine with an amino group, separated into individual anomers, and the β-anomer

• phosphate 12a or another route for its generation. Yamada et al. studied in detail the transformation of the fluoride 9 in a 3:1 mixture of the α- and β-anomers of the phosphates 12a and 12b. They employed this mixture in the condensation with adenine and 2,6-diaminopurine catalyzed by PNP from Bacillus

• white powder in 42–50 % yield. The structures of the α- and β-anomers 12a and 12b were verified by a careful analysis of the 1H and 13C NMR spectra {[1H,1H] and [1H,13C] 2D COSY and NOESY spectra} as well as by the 19F and 31P NMR and by comparison with published 1H and 13C NMR data for the α-anomer 12a

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• group participation of the 2-O-acetyl protecting group, afforded the desired anomers in good yields. The trichloroacetimidate intermediate was formed to enhance coupling. Syntheses of the carbohydrate-functionalized dendrimers were performed by addition of compound 1 as shown in Scheme 2. The

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• interaction between the receptor and octyl α-D-mannoside (the receptor binds strongly both α and β anomers [12]) was also studied in these two solvents. These two approaches intend to address two working hypothesis: the receptor is active in acetonitrile but not in water due to the different conformational

Synthesis of a derivative of α-D-Glcp(1->2)-D-Galf suitable for further glycosylation and of α-D-Glcp(1->2)-D-Gal, a disaccharide fragment obtained from varianose

• Carla Marino,
• Carlos Lima,
• Karina Mariño and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2012, 8, 2142–2148, doi:10.3762/bjoc.8.241

• α/β ratio. The anomeric signals were observed at δ 5.55 (dd, H-1α) and 5.50 (d, H-1β) and after D2O exchange they were simplified to a doublet and a broad singlet, respectively. The 13C NMR spectrum of 8 showed signals at 97.2 and 96.7 ppm for the glucopyranosyl unit of both anomers and signals at δ

• 100.4 and 99.3 for C-1 of the β and α-anomers, respectively. Derivative 8 is ready to be activated by the trichloroacetimidate method, for the synthesis of larger oligosaccharides. Conventional de-O-benzoylation and subsequent hydrogenolysis of 8 afforded disaccharide 1 in good yield (Scheme 1). The NMR

• spectra of 1 showed equilibrium between the disaccharide with the reducing end in the pyranosyl and a lower amount in the furanosyl configuration. Thus, the 13C NMR spectrum showed resonances at 97.9 and 96.1 ppm, corresponding to C-1’ and signals at 96.6 and 89.6 ppm, due to C-1 of both anomers of α-D

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• anomeric ratios (2A: α/β 9:1; 2B: α/β 20:1). The azido group was easily reduced and concomitantly acetylated to establish the N-acetyl group in the C2 position with thioacetic acid in the presence of pyridine [24][25]. The anomers could be easily separated at this stage by column chromatography. In the

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• hydroxy nucleophile on the central glucosamine. Our first attempt to glycosylate using fucose thioglycoside building block 25 afforded the product in low yield and as a mixture of anomers as confirmed by LC–MS analysis. The use of N-phenyl trifluoroacetimidate building block 24 proved more efficient

• . Nevertheless, when fucosylation with building block 24 was performed in dichloromethane, a mixture of anomers of compounds 26 was detected by NMR analysis. Only running the reaction in ether, which is a strong α-directing solvent [28], ensured stereoselective introduction of the fucose residue. Under these

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• (−30 °C). Under these conditions, the desired trisaccharide 26 was isolated in 78% yield but as an 8:2 mixture of the α and β-anomers as estimated by 1H NMR. Although the desired anomer 26α could be obtained pure upon purification by HPLC, it was isolated in a less than desirable yield of 48%. We thus

Synthesis and antifungal properties of papulacandin derivatives

• Marjolein van der Kaaden,
• Eefjan Breukink and
• Roland J. Pieters

Beilstein J. Org. Chem. 2012, 8, 732–737, doi:10.3762/bjoc.8.82

• -H, followed by oxidative spiroketalization under basic conditions to give the α- and β-anomers 29, which were separable using column chromatography. However this was not necessary: The β-anomer could readily be converted into the more stable α-anomer 32 by using a solution of 0.1 M HCl in chloroform

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• , justifying a more profound conformational analysis of this product (Figure 6). Conformational molecular dynamics runs (MD) were performed on both anomers of the two regioisomers of 8d to simulate the behavior of the molecule during more than 5000 ps of molecular motion. Thereby, it was found that for the

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• protected by the silylation with hexamethyldisilazane. Subsequently, this modified uracil was reacted with protected 2-deoxyribose in the presence of SnCl4. Finally, protected α- and β-anomers 111 and 109 were treated with methanolic sodium methoxide to afford the nucleosides 112 and 110. Synthesis of

Carbasugar analogues of galactofuranosides: α-O-linked derivatives

• Jens Frigell and
• Ian Cumpstey

Beilstein J. Org. Chem. 2010, 6, 1127–1131, doi:10.3762/bjoc.6.129

• common than their β-linked anomers, from which they are distinguished by their 13C C1 chemical shifts (α, 103.8 ppm; β, 109.9 ppm for the methyl glycosides) [3], and 3J1,2 1H,1H coupling constants (α, 4 Hz; β, 2 Hz) [4]. Nevertheless, α-galactofuranosides occur as components of a number of

Preparation of aminoethyl glycosides for glycoconjugation

• Robert Šardzík,
• Gavin T. Noble,
• Martin J. Weissenborn,
• Andrew Martin,
• Simon J. Webb and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2010, 6, 699–703, doi:10.3762/bjoc.6.81

• glycosylation reactions are summarised in Table 1. Fully protected xylopyranoside 10 could be prepared both from the corresponding bromide as well as the acetate (the β-anomer was prepared from xylose with sodium acetate in acetic anhydride) in similar yields. In each case both anomers were formed with moderate

• the product was difficult to separate from starting materials, in particular the N-Cbz-aminoethanol. With Hg(CN)2, or the more reactive Hg(CN)2/HgBr2-mixture, in dichloromethane or acetonitrile, glycosylation was more successful, but both anomers were generated. Given the problems previously

• . Attempts to speed up the reaction by heating led to the observation that in acetonitrile predominantly one (β) anomer is formed, but anomerisation occurs with longer reaction times. In dichloromethane both anomers were formed. The best reaction conditions were combined to give Method A. The success of

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• activities, probably due to the presence of a hydrophilic sugar substituent at the nitrogen atom of the nor-tropane ring [71][72]. Several groups have shown that disaccharide ureas and carbamates with different bridging positions as α/β-anomers are readily accessible by the coupling reaction of aminosugars

Benzyne arylation of oxathiane glycosyl donors

• Martin A. Fascione and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2010, 6, No. 19, doi:10.3762/bjoc.6.19

• occasion as a 96:4 (α:β) mixture of anomers (Scheme 4d). This slight drop in stereoselectivity is consistent with the increased reactivity of benzylated relative to acetylated thioglycoside donors [13][32], commonly attributed to greater stabilisation of the developing positive charge on an oxacarbenium

Recognition properties of receptors consisting of imidazole and indole recognition units towards carbohydrates

• Monika Mazik and
• André Hartmann

Beilstein J. Org. Chem. 2010, 6, No. 9, doi:10.3762/bjoc.6.9

• observed for 4 and 5 are quite different to those of the recently described phenanthroline/aminopyridine-based receptors 22 and 23 (see Figure 4) [27][29], which show a strong preference for α-glucoside and α-galactoside vs. the β-anomers. Thus, depending on the nature of the recognition units used as

• and 5 with these monosaccharides to be much more favorable than those with the α-anomers 7a and 9. The curve fitting of the titration data for 4 and β-glucoside 6a suggested the existence of 1:1 and 2:1 receptor–sugar complexes in CDCl3 solutions with a stronger association constant for 1:1 binding

Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

• Pitak Nasomjai,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2009, 5, No. 37, doi:10.3762/bjoc.5.37

• -phosphate is described. Preparations of both the α- and β-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each α-ribose is also reported. These compounds have been prepared as tools to probe the details of

Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: Exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives

• Andrew Kennedy,
• Adam Nelson and
• Alexis Perry

Beilstein J. Org. Chem. 2005, 1, No. 2, doi:10.1186/1860-5397-1-2

• substitution under the reaction conditions. In each case, the required products (26 and 30) were obtained in moderate (30–37% i.e. 67–71% per step) yield over the three synthetic steps as 66:34 mixtures of anomers. Nevertheless, the yields were deemed acceptable because, over the three steps, significant

• highly (>95:<5) diastereoselective. Fortunately, the anomers of the bis-allylic alcohols 27, 29 and 33 were separable by careful column chromatography. The stereochemical outcome of the Luche reduction had been remarkable: although the reaction had been highly diastereoselective in both heterocyclic