Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• ]octane, while O6 migrated when the C4–OH was axial leading to 2,4-dioxabicyclo[2.2.2]octanes. The formation of both anomers from the non-selective addition of fluoride suggested intermediates with oxocarbenium character. This work has recently been extended by Banwell and co-workers to include a set of

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• . While no direct interactions with the protein backbone were observed, we found one water molecule to mediate hydrogen bonding between the oxygen of the N-acetyl group and the Asn43 side chain oxygen (Figure 4d). Both GalNAc anomers could be observed, showing interactions through water molecule

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• using established procedures from the literature, commencing with ᴅ-glucosamine and benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-ᴅ-glucopyranoside as the starting materials, respectively [40][41][42][43]. Imidate donors 1a and 1e were obtained exclusively as α-anomers, and 1b and 1g as a 1:1 α:β

• mixture which were then purified to give the desired α-anomers. Thioglycosides 1c, 1d, and 1f were isolated purely as β-anomers due to anchimeric assistance from the C2 N-acetyl or N-Troc groups. In glycosyl acceptors, the first amino acid of the lipid II pentapeptide, Ala, was incorporated as a 2

• -anomers of compound 5. It is noteworthy to mention that the benzyl ether in compound 4 exhibited successful cleavage upon treatment with sodium bromate/sodium dithionite in ethyl acetate/water, while other protecting functionalities like acetyl and phenylsulfonylethyl ester groups remained intact [45

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• the stereoselectivity of sialylation, it is important to analyze anomeric ratio values (α/β) for the disaccharide fraction separated by size-exclusion chromatography since the retention values of different disaccharide anomers on silica gel may be surprisingly large and a minor isomer may be lost

• -acetyl groups. The disaccharide fraction was isolated by gel permeation chromatography on Bio-Beads S-X3 (toluene) and analyzed by 1H NMR spectroscopy to give the anomeric ratio (α/β). Individual anomers of disaccharides were then separated by silica gel chromatography to give the yield. Model

GlAIcomics: a deep neural network classifier for spectroscopy-augmented mass spectrometric glycans data

• Thomas Barillot,
• Baptiste Schindler,
• Baptiste Moge,
• Elisa Fadda,
• Franck Lépine and
• Isabelle Compagnon

Beilstein J. Org. Chem. 2023, 19, 1825–1831, doi:10.3762/bjoc.19.134

• four monomers is shown in Figure 2. Note that both α and β-anomers coexist in the experimental conditions. The second set of experimental MS–IR spectra was acquired using different instrumental conditions on a different experimental set-up: it consists of the coupling of an alternative design of mass

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• known as (±)-BCH-189 (1c). The key oxathiolane 4, a precursor of the corresponding nucleoside, was obtained as a 1:1 mixture of anomers (60%) from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na. The reaction was performed in toluene in the presence of p-toluenesulfonic acid

• , which was subsequently acetylated with acetic anhydride to afford 8 as a 2:1 mixture of anomers. Chu and co-workers [40] applied a novel strategy for the synthesis of enantiomerically pure (+)-BCH-189 (1a) using ᴅ-mannose (3c) as a starting material (Scheme 3). 1,2,3,4-Tetraacetyl-ᴅ-mannose derivative 9

• treated with acetic anhydride at room temperature. After workup by adding water and diethyl ether, the reaction mass was filtered and distilled until a residue was obtained. The colorless liquid compound 8 was obtained in 64% yield (as 6:1 mixture of anomers) after flash chromatography with 20% ethyl

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• recognition by plant cell-wall antibodies. To avoid performing the challenging 1,2-cis glycosylation that would generate a mixture of anomers in AGA, the α(1–6) linkage between glucose and xylose was pre-installed in the disaccharide BB 16 (Scheme 3, highlighted in red) [104]. The orthogonal levulinoyl (Lev

• dramatic when 2,4-di-O-acyl groups are present, sometimes leading to exclusive formation of α-anomers [128][129]. PGs like 2-O-ADMB (4-acetoxy-2,2-dimethylbutanoate) [130] or 2,2’-O-benzylidene [131] were introduced to solve this issue. Several reports highlighted the importance of the 4,6-O-benzylidene

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• and 12 under these conditions produced the expected thioglycosides 18 and 19, respectively. Difluorinated derivative 13 decomposed on reaction with the PhSTMS/ZnI2 system. The separation of the anomers of products 14–19 was attempted because of the risk of thiophenyl migration in the subsequent C6

• deoxyfluorination, which would likely occur with the β-anomers of 14–19 [41]. The complete separation of the α-anomer by conventional silica gel column chromatography was possible for thioglycosides 14, 16, 17, and 19, while the products 15 and 18 were obtainable as enriched α-anomers (α/β ≥ 3.3:1). Cleavage of the

• sulfurtrifluoride (DAST) [51], but our experiments revealed that DAST-mediated C6-deoxyfluorination of thioglycosides 14–17 and 19 proceeded satisfactorily under microwave irradiation, on condition that pure or substantially enriched α-anomers were subjected to reaction with DAST, yielding thioglycosides 22–26

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• glucosyl fluoride gave better yields (18a and 18d) than with the corresponding acylated analogues β-9 and α-11 described above. It was also found that the glycosylation stereoselectivity with glucosyl fluoride 16 did not depend on the anomeric ratio of glucosyl fluoride 16: both anomers of 16 yielded

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• , sugars, and are read from right to left starting with the base (reducing-end) sugar. The letters a and b are reserved for α and β-anomers, respectively, while brackets are used to delimit branches, and the letter T is used to denote the connection point to ceramide, or to another conjugate depending on

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• could then be opened under acidic conditions [22] to give the acetyl pyranoside 4 as a mixture of two anomers (α:β: 1:0.5) in a 95% yield. The methyl glucoside 5 was prepared by treating acetyl glucopyranoside 4 with methanol and HCl to generate an anomeric mixture of the methyl glucopyranoside 5. By

• group has earlier been used as metal chelator [25]. At this stage, it was possible to separate both anomers of the diazide 18 using flash column chromatography. The pure α-anomer was then subjected to a CuAAC reaction using 1-heptyne and, in only two steps, the new surfactant 19 could be prepared from

• conformation as discussed earlier. Conclusion In conclusion, it was possible to convert levoglucosan into building block 5 in only five robust steps. The building block 5 could be purified to afford the two pure anomers using column chromatography. The β-anomer, 5β, proved to be a very versatile template for

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• -tagatofuranoside 13 in satisfactory yield (Scheme 3). In the course of the thioglycosylation, only the α-anomer of 13 was detected and isolated as the product. In general, the formation of α-anomers during the thioglycosylation of di-O-isopropylidene-ᴅ-tagatofuranoses 11 and 12 was controlled by the approach of a

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• reducing-end monosaccharide 14 equipped with the linker in 70% yield as a mixture of anomers (α:β = 2:1) (Scheme 2). The reductive opening of the benzylidene protecting group in 14 enabled the separation of anomers and furnished acceptor 15α [28], that was reacted with thioglucoside 11 to yield exclusively

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• glycosylamines 2a–f by hydrogenation with Pd on charcoal in ethyl acetate. Since an anomeric mixture of glycosylamines was obtained in most cases, with a strong predominance of the corresponding β-anomers, and TLC analysis showed no formation of other unwanted side products during hydrogenation, the latter

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• β-ᴅ-Galp was also observed [33]. For donor 3, there was no major difference between benzylated (1α/β) and benzoylated acceptors (2α/β), and the regioselectivity was higher for the α-anomers (compare Table 1, entries 1 and 2 or 3 and 4, for example). The low nucleophilic character of the OH-4 group

• in α-anomers could be associated with the lower capacity of the O-5 atom to establish hydrogen bond interactions due to the anomeric effect [34]. For donor 4, the regioselectivity observed for 1α, 1β, and 2α was lower than that observed for 3, but for 2β, the only product detected was the 1→4

• accurate prediction of the trends in selectivity could not be achieved. We have tried to explain the reduced regioselectivity of the β-anomers through hydrogen bonding interactions of the OH-3 and OH-4 groups of the model acceptors. Doutheau and co-workers proposed that such a reduced regioselectivity

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• (10), forming gels much easier than their corresponding β-anomers (trans). This showed that their ability to form gels was critically dependent on the cis/trans configuration present in the molecule. To confirm this result, the supramolecular properties of trans- and cis-1,2-bis(4-(4-bromophenyl)-1H

Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• -acetylation was conducted leading to a mixture of all four species, indicated by NMR analysis (Scheme 3). In the case of 2-syn the β-pyranose species 5-syn-β was obtained as the main product, besides α-pyranose (5-syn-α) as well as both anomers of the furanoid form (Scheme 4). The overall yield obtained over

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• dried over MgSO4 and the solvent removed under reduced pressure. The crude product was purified by column chromatography (petroleum ether/ethyl acetate 1:1) to yield Ac4ManNCp(H2) (302 mg, 34%) as a mixture of anomers as a colorless solid. Whereas the α-anomer could be partially separated by column

• chromatography (petroleum ether/ethyl acetate 1:1) to yield Ac4ManNCyc(H2) (473 mg, 52%) as a mixture of isomers (anomers as well as cyclopropane isomers indicated as a and b) as a colorless solid. Whereas the α-anomers could be partially separated by column chromatography, semi-preparative RP-HPLC (50–55% B

• over 20 min) was required to obtain β-anomers (tR = 12.3 min). Rf = 0.54 (petroleum ether/ethyl acetate 1:2); α-isomer: 1H NMR (400 MHz, CDCl3) δ 6.07 (d, J = 1.8 Hz, 1H, H-1a), 6.04 (d, J = 1.9 Hz, 1H, H-1b), 5.86–5.72 (m, 1H, NH), 5.36–5.28 (m, 1H, H-3), 5.28–5.12 (m, 1H, H-4), 4.69–4.57 (m, 1H, H-2

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

•  1 shows the detailed reaction conditions for methanol, propargyl alcohol and 4-pentynol. The two-step reaction starting from pyranose 4 gave overall yields in the range from 43% to 69%. Due to the neighbouring group participation of the acetyl group at C-2, only β-anomers of the respective

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• modifications which have been undertaken on the nicotinoyl riboside scaffold. Keywords: anomers; glycosylation; isotopologues; isotopomeres; nicotinamide riboside; Review 1. Introduction 1-(β-D-Ribofuranosyl)nicotinamide (also referred to as nicotinamide riboside, NR+) is one of the multiple precursors of

• riboside anomers were synthesized, with the best β/α-anomer stereoselectivity obtained when the chloride form of the sugars were used as precursors. Thus, the reaction between Nam (1a) and 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride (3a) in acetonitrile at 0 °C yielded the triacetylated product 4a mainly

• yield. The anomeric purity of the acylated intermediates 4a and 4b was not reported in [20]. However, these triesters must have contained some admixture of α-anomers as evidenced by the optical rotation of the final product NR+Cl−. The corresponding nicotinamide mononucleotide (NMN) was prepared from NR

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• enlargement via selective cyclopropane ring opening [46][47][48][49]. Consequently, the synthesis started from the previously described bicyclic silyl enol ethers 1α/β (Scheme 1) [50][51]. The two anomers of 1 were individually transformed into the trimethylsilyl (TMS)-protected sugars 2α/β by adapting and

• persilylated thymine in the presence of NIS (Scheme 2), followed by radical reduction of the iodide intermediate with tributyltin hydride (Bu3SnH) generated an anomeric mixture of nucleoside 6α/β with the β-anomer as major component (α/β ratio = 1:4.5 according to 1H NMR). The inseparable anomers of nucleoside

• 6α/β were subjected to the next reaction step, where the simultaneous desilylation and cyclopropane ring opening to the bicyclic fluoroenone 7 occurred. HF-pyridine smoothly facilitated this conversion. At this stage the two anomers of fluoroenone 7 were separable. The configurational assignment of

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• proceeded mostly in good to high yields (57–86% for the Ritter reaction and 35–89% for the Ullmann coupling). The Ritter reaction gave two anomers, which could be separated by column chromatography. The prepared ligands showed promising results (er of up to 84:16) in Tsuji–Trost reactions with diphenylallyl

• is hindered. In the literature this fact is used to explain the different reactivities between “armed” and “disarmed” glycosyl donors in glycosylation reactions [33]. Due to the fact that 9 can be attacked from two sides by nitriles, the oxazolines occur in two isomeric forms, the β-anomers (10) and

• the α-anomers (11), which were separated by column chromatography. No crystals suitable for X-ray crystallography could be obtained from the direct products of the Ritter reaction. To get a more polar molecule which is more appropriate to form crystals suitable for X-ray crystallography, a deprotected

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• equilibrium of both, α- and β-anomers (Scheme 2, right dashed box). However, full anomerization is often not observed as the rate and the extent of mutarotation depends on various parameters such as anchimeric effects of neighboring groups and the reaction conditions. Hence it has been frequently observed in

• employed acidic reaction partner can lead to predominant formation of the β-configured product, whereas stronger acidic reagents can favor the formation of the respective α-anomers. These findings can be explained by considering the two different reaction pathways A and B as shown above in Scheme 2. The

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• under sila-Pummerer conditions [29][30]. We found that treatment of 12, obtained by oxidation of 11, with excess persilylated N4-acetylcytosine in the presence of TMSOTf as a Lewis acid gave an inseparable mixture of α- and β-anomers of 4’-thioDMDC derivatives 15 in good yield. Based on the study of the

• reacted with a nucleobase, giving a mixture of α- and β-anomers since the reaction might occur by the simple SN2 reaction. Thus, the reaction proceeded through both paths a and b in method A, but path a was predominant in the reaction of method B [45] (Figure 3). Nishizono et al. applied the hypervalent

• ). The hypervalent iodine-mediated glycosylation of 2,4-bis(trimethylsilyl)uracil (29) with glycal 124 gave an inseparable mixture of α- and β-anomers 125 (α:β = 1:2) in 51% yield as we expected. Compound 125 was then oxidized by treatment with mCPBA, followed by elimination of the resulting selenoxide