Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• conditions. The hydrogen sulfide ion is 105 times less basic than the hydroxide ion and, hence, able to compete with the sugar oxyanions as a leaving group upon breakdown of the thiophosphorane intermediate (the bond energies of P–O and P–S bonds are 86 kcal mol−1 and 55 kcal mol−1, respectively [103

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• maneuver stereochemistry as well as to incorporate structural modifications. In this review, we describe recent reports on the modular synthesis of C-nucleosides with a focus on D-ribonolactone and sugar modifications that have resulted in potent lead molecules. Keywords: C-nucleosides; convergent

• and supramolecular complexes [10][11][12][13][14][15][16][17][18][19][20][21][22]. Nucleic acids are composed of a monomeric nucleoside unit that features an aromatic nitrogenous moiety (a nucleobase) connected to a pentose sugar, which in turn is attached to a phosphate group (Figure 1) [7]. The

• pentose sugar and the nucleobase are connected by a carbon–nitrogen bond that is adjacent to the sugar oxygen resulting in an hemiaminal ether bond, also known as the glycosidic bond. Because of their key role in many biological processes, modifications to the nucleoside structure have been widely

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• . In a similar fashion using 10 mol % AuBr3, 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl azide (2) and 2,3,4,6-tetra-O-acetyl-β-D-mannopyranosyl azide (3) were obtained from their corresponding per-O-acetylated sugar precursors (Table 1, entries 1 and 2) in 3 h at 25 °C in 87% and 90% yield

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• pocket. Both of these terminal sugar residues show hydrogen bonding interactions with the protein and associated water molecules. The GM1 oligosaccharide (GM1os) binds very tightly to CTB with a dissociation constant (Kd) of around 40 nM (measured by isothermal titration calorimetry, ITC), while simple

• linker emerging through the central channel. c) Close-up view of the two sugar binding sites. Figure prepared using the PyMOL programme from Protein Data Bank files 1XTC.pdb, 3CHB.pdb and 3EFX.pdb. Bernardi and co-workers’ designed oligosaccharide mimetics of GM1. Structure of monomeric ligands. X

• -bifunctional inhibitor designed by Bundle and co-workers. Glycopolymers with exchangeable sugar ligands and variable length linkers. Acknowledgements This review is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• the modification in the nucleotide: the internucleosidic phosphate, the nucleobase, the sugar or the extremities of ONs. Moreover, the review provides a current and detailed account of stimuli-responsive ONs with the main goal of gene silencing. However, for some stimuli-responsive ONs reported in

• ) backbone in the replacement of the phosphate ester internucleotide linkages. This modification provides nuclease stability and favorable pharmacokinetic properties but can lead to some toxicity. In addition, the most extensively used sugar modifications are represented by the 2’-modifications: 2’-O-methyl

• , their gene silencing effects were weaker than those of PS AONs when tested using the same model assay. It seems that the conversion of the modified ONs into native ONs might occur too slowly inside cells to improve gene silencing. Modifications at the sugar 2’-OH Several permanent 2’-O-modifications (2

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• chloride (DMC), and related reagents, which can direct convert an oligosaccharide with a 2-acetamido sugar at the reducing terminus directly into the corresponding oxazoline in water. Therefore, oxazoline formation can now be achieved in water as the final step of any synthetic sequence, obviating the need

• protected (typically peracetylated) GlcNAc or other 2-acetamido sugar [37][38][39][40]. Oxazoline formation is achieved by activation of the leaving group at the anomeric centre and neighbouring group participation by the 2-acetamide. Unfortunately application of these reaction conditions to oligosaccharide

• substrates leads to significant cleavage of interglycosidic linkages, and correspondingly low yields of products. However, two methods that are useful for the production of oligosaccharide oxazolines are treatment of the peracetylated sugar with either TMSOTf in dichloroethane [39], or with TMSBr, BF3·Et2O

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• oligonucleotide mimics that consist of a peptide-like backbone. Although the idea of replacing the whole sugar-phosphate backbone of DNA with a completely unrelated scaffold such as peptide had been around since the 1970s [20], it was not until the 1990s that the first PNA system with an N-2-aminoethylglycine

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• analogues The development of synthesis methods of nucleobase analogues remains a challenge. This is mainly due to the presence of multiple reactive functional groups both on the nucleobase as well as the sugar moiety and requires the introduction of orthogonal protection groups. A careful consideration of

• synthesis of tCnitro followed the procedure of Roth et al. [39] to furnish the aromatic core 13 (Scheme 3). Compound 13 was then glycosylated by making the sodium salt and reacting it with Hoffer´s α-chloro sugar yielding 14 in 11% yield after isolation [46]. The p-toluoyl protection groups were cleaved by

• sodium-salt method [42]. The deoxyribosylation was then achieved using the same Hoffer’s α-chloro sugar, but in presence of a Lewis acid yielding the protected nucleosides 19a–c [48]. The cleavage of the protection groups was achieved with sodium methoxide to furnish compounds 20a–c. The improved

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• derivatives are optically active. The π→π* transitions of the bases (Scheme 1) contribute to the electronic circular dichroism mostly as a result of the chiral perturbation exerted by the sugar moiety. The ECD signals of single nucleosides/nucleotides are, accordingly, quite small. Coupling into

• vibrational modes of the sugar moieties. The VCD appearing in this region is less dependent on the base composition [42]. 5.2. Practical information Choice of solvent and sample cell: Although the analysis of biomolecule interactions is best performed

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• attach these sugar-containing thiol ligands to AuNPs [70][71][72][73], there has so far only been one study that reported the use of the CuAAC to click sugars directly onto the surface of AuNPs. In 2008, Chikae et al. reported the use of CuAAC to react alkyne-terminated thiol-functionalized AuNPs that

• with carbohydrates using the azide–alkyne Huisgen cycloaddition. The three major methods for the synthesis of GAuNPs. (a) Direct reduction of an Au3+ salt in the presence of thiol-linked sugar derivatives to obtain GAuNPs of sizes smaller than 10 nm. (b) Exchange of citrate molecules (cit) on citrate

• -stabilized AuNPs with thiol-linked sugar derivatives to obtain GAuNPs of various sizes. (c) Reactions of AuNPs (obtained after ligand exchange) with suitably functionalized sugar derivatives. The non-catalysed azide–alkyne Huisgen cycloaddition (NCAAC) between an organic azide (1,3-dipole) and an alkyne

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• crucial class of biomolecules such as oligosaccharides and glycoconjugates, where one sugar unit is linked with another sugar unit or any other molecules (aglycons) [1][2][3][4]. Owing to their high importance, several efficient protocols have been developed for the stereoselective glycosylation in the

• catalyst loading and produced the desired glucosides 5j–m, respectively, in moderate to good yields (43–67%) and with good α-selectivity (Table 2, entries 9–12). As expected, on treatment with a sugar-based acceptor such as 1,2:3,4-di-O-isopropylidene-D-galactose (2n), the corresponding glycoside 5n was

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• , particularly antifungal [3][4][5][6] and antitumor [7][8][9]. The aglycone part of a saponin is termed sapogenin. Diosgenin, yamogenin, tigogenin, smilagenin and sarsapogenin are the most abundant sapogenins in nature [10]. They are linked via a glycosidic bond to a sugar unit, mainly D-glucose. Diosgenyl

• the condensation of saccharides with ureas or the reaction of glycosylamines, amino sugar, or aminoglycosides with isocyanates, or their equivalents such as carbamates [32][33]. Ureido saponins presented here were obtained in the reaction of ethyl isocyanate (8), chloroethyl isocyanate (9) and phenyl

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• suppressing its aggregation property. It is also necessary to improve the water solubility of the lipophilic phthalocyanine in order to increase its biocompatibility [88][89]. One frequent method to increase the water solubility of phthalocyanine involves the combination of a biomolecule such as a sugar [90

Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

• Magdalena Ceborska,
• Magdalena Zimnicka,
• Aneta Aniela Kowalska,
• Kajetan Dąbrowa and
• Barbara Repeć

Beilstein J. Org. Chem. 2017, 13, 2252–2263, doi:10.3762/bjoc.13.222

• α-glucopyranoside (Δδ = 0.04–0.07 ppm, Supporting Information File 1, Figure S4, Table S2). This strongly supports the assumption that the PTX dianion interacts with hydroxy groups of the sugar moieties, and this phenomenon was already highlighted in the literature [23][24]. Keeping in mind that

• from NMR experiments performed for PTX mixtures with CDs simplest analogue – methyl α-D-glucopyranoside showed that PTX dianion interacts with hydroxy groups of sugar moieties. This additionally proved that unusually large changes of chemical shifts for PTX upon addition of α-CD were caused by carboxyl

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• the coupling of two simple monosaccharides and subsequent transformation of the resulting enone into the protected C12-sugar 1. The conversion of the latter into alditol 2 allowed us to prepare derivative 3 having a 18-membered ring (Figure 1) [8]. Higher sugar 1 has a substantial synthetic potential

• in diol 2 is not possible. Thus we decided to differentiate the terminal positions in the stage of higher sugar 1. The replacement of the hydroxy group at the C12-position with an azide, accomplished successfully under Mistunobu conditions, afforded azide 4 in 95% yield (Scheme 1). The crucial step

• was the liberation of the anomeric position (C1), which, as we noticed, can cause problems. We subjected azide 4 to acetolysis and, although this reaction is very capricious in higher sugar chemistry [7][8], succeeded in the preparation of the desired hemiacetal acetate 5 in very good yield (86%) as a

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

• Neha Rana,
• Manish Kumar,
• Vinod Khatri,
• Jyotirmoy Maity and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205

• : bicyclonucleosides; biocatalysis; lipase; Novozyme®-435; separation of epimers; Introduction Sugar-modified bicyclic nucleosides have drawn the attention of synthetic chemists because of their effect on the conformational restriction of the furanose moiety of the nucleoside [1][2][3][4][5][6][7][8][9]. The

• ribo-trihydroxy sugar derivative starting from diacetone-D-glucose led to the formation of an inseparable 1:1 mixture of the required compound and its C-3 epimer, i.e., 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose [10]. Lipases have been used extensively for the selective manipulation of

• hydroxy groups present in different sugars and sugar moieties of synthetic or naturally occurring glycosides, nucleosides, etc. Gotor et al. [11] have reported a lipase-mediated acylation of an equimolecular mixture of D/L-thymidine with acetonoxime levulinate as acylating agent and Pseudomonas cepacia

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• (1→4) glycoside.” Indeed, after sequential glycosylation in the presence of TsOH at 50 oC, methanolysis, and per-acetylation, disaccharide 4 was isolated in 20% yield. The authors then very reasonably concluded that “Consequently, the presence of the ester linkage which kept the two sugar moieties in

• disaccharide 9 in 74% as a pure 1,2-trans isomer [52]. Expansion of this approach to other positions and sugar series showed that the stereoselectivity could be relaxed, and seemed to be dependent of the donor–acceptor match–mismatch. Thus, when succinoyl was attached to the 6-OH of the galactosyl acceptor

• category was extensively studied and applied to a variety of sugar series and targets [58][73][74]. Phthaloyl and related tethers Phthaloyl tethering was also introduced by Ziegler [53] and practically concomitantly by Valverde et al. [54] as “template-directed cyclo-glycosylation.” In the latter

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• group at C-6 and C-4 position, respectively. The DBDMH/TfOH system activates glycosyl donors including neutral monosaccharides of different configurations (D-gluco 5 and 6, D-galacto 1 and 4, D-manno 8, L-rhamno 9), amino sugar 7 and uronic acid 10. All thioglycosides reacted equally well, irrespective

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• current enzymatic methods described for the synthesis of unusual C- and S-glycosidic linkages, their mechanisms and the corresponding perspectives. Review Glycosyltransferases Glycosyltransferases (GTs, E.C. 2.4.1.x) catalyse the addition of a glycosyl moiety to an acceptor, using an activated sugar as

• sugar during GT-catalysed reactions, GTs are also classified as inverting or retaining (Figure 1). Inverting GTs operate via a SN2 mechanism in a single displacement step where an acid/base residue enhances the nucleophilicity of the acceptor, via an oxocarbenium-like transition state. Unlike inverting

• aggression. Their biosynthetic pathway requires the action of a S-GT (UGT74B1) that catalyses the reaction between a thiohydroximate acceptor and UDP-α-D-glucose as sugar donor to yield the corresponding desulfoglucosinolate (Figure 2) [20][21]. UGT74B1 from A. thaliana is a versatile enzyme in terms of

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• sugar moiety [6]. Many of them concern the C-2’ and C-3’ sugar positions. However, functionalization at C-5’ has been much less reported, particularly the stereocontrolled formation of a stereogenic center at C-5’, in spite of its important role for biological activity (Figure 1) [16][17][18][19]. In

2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization

• Julia Kinzel,
• Daniel F. Sauer,
• Marco Bocola,
• Marcus Arlt,
• Tayebeh Mirzaei Garakani,
• Andreas Thiel,
• Klaus Beckerle,
• Tino Polen,
• Jun Okuda and
• Ulrich Schwaneberg

Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148

• membrane of Escherichia coli (E. coli) [30]. For extraction of membrane proteins, commonly micelle-forming detergents such as sodium dodecyl sulfate (SDS), polyethylene–polyethyleneglycol (PE–PEG), sugar glycosides or polyoxyethylenes are applied [24][25][28][31][32]. SDS is an efficient detergent for

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• 1-O-phosphofuranosyl hexoses in good to excellent yield (Table 1, entries 1–4) [43]. The conditions provided only a very modest stereoselectivity, however, the α anomer was slightly favored regardless of the stereochemistry of the sugar at C2. Most importantly, very little or no ring expansion to

• 1,6-anhydrosugars: The treatment of a 2-deoxy-2-N-acetylated sugar with DMC and an amine base in the absence of any nucleophile provides the observable (by 1H NMR) or even isolatable (LacNAc) corresponding oxazoline derivative in moderate to very good yield (Scheme 21, pathway A) [68][69]. It is

• transformations as well. Under the same conditions but using a C2–OH sugar, the corresponding isolatable 1,6-anhydrosaccharide is formed in good to excellent yield [71]. The authors proposed as the intermediate species the unstable 1,2-anhydrosaccharide resulting from nucleophilic displacement of the activated

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• -anhydro-α-L-galactopyranose unit (naturally present in the agarose structure) to all glycamines synthesized, constituting an amino-substituted C-threofuranoside moiety, which is closely related to (+)-muscarine. Keywords: amino sugar; 3,6-anhydro-α-L-galactopyranose; polysaccharide (agar); protecting

• exchange resin, which by eliminating acetate ions enabled the elimination of remaining ammonia by reduced pressure evaporation. The amino sugar rich fraction was then concentrated and chromatographed on silica gel using MeOH/2 M NH4OH as mobile phase. An aqueous solution containing the isolated free-base

• ). By performing the reductive amination between 2 and dimethylamine hydrochloride we obtained a mixture of epimers (8 and epi-8) which differed on the stereochemistry of the C-2 of the 3,6-anhydro amino sugar moiety. This was related to the fact that during the course of the reductive amination, the

Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded silver nanoparticles for catalytic reduction

• Qing Yin,
• Qi Chen,
• Li-Can Lu and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 1212–1221, doi:10.3762/bjoc.13.120

• reduction of 4-nitrophenol (4-NP) with an activity factor ka = 51.4 s−1 g−1, which is higher than some reported AgNP-containing composite materials. Keywords: catalytic reduction; hypercross-linking; porous polymers; silver nanoparticles; sugar; Introduction Hypercross-linked polymers (HCPs) are

• ]. The chemical structure of monosaccharides is commonly a polyhydroxylated aldehyde or ketone with a pyranose ring structure. These hydroxy groups can be easily benzylated to afford sugar-based monomers containing multiple aromatic skeletons. Recently, Liu and Dai have reported a class of novel

• molecules into the holes with the catalyst active sites [38][39]. Therefore, it is of great interest to improve the catalytic efficiency by encapsulating the nanocatalyst in a porous organic polymer. Keeping these issues in mind, three novel sugar-based porous organic polymers SugPOP-1–3 were designed and