Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• , adamantylglycine (AdGly), bound to the N-terminus of ʟ-Ala-ᴅ-isoGln dipeptide part as well as their mannosylated derivatives. Different isomers of mannosylated adamantyl tripeptides, regarding the chiral centers introduced at adamantylglycine and spacer which connect the sugar part to the adamantyltripeptide were

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• the serine residue and the amide proton of GalNAc unit [33]. This correlates with our results obtained for longer peptides containing the same sugar moiety attached to threonine. Moreover, Corzana et al. [33] highlighted the importance of surrounding solvent molecules, which are responsible for the

• peptide 3 (see Table 3 and Figure 4). Such situation is the result of numerous well defined intra- and interresidual NOE signals of sugar moiety protons (see Table S6, Supporting Information File 1). Although the orientation of the galactose ring is highly ordered, as shown the value of the temperature

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• suitable agents for boron neutron capture therapy (BNCT) became a major need. Among many others, sugar boronic acids have recently attracted attention as boron carriers. Herein we report the synthesis and preliminary biological studies of two new sugar analogues containing a boronic acid at the anomeric

• position. The analogues were obtained by hydroboration of proper open-chain terminal alkenes that, after quenching with water, spontaneously afforded cyclic boronic acids with hemiacetal-like structures. Keywords: antitumor agents; boron neutron capture therapy; boronic acid; hydroboration; sugar analogue

• boron-containing carbohydrate derivatives for BNCT has received special attention because of the sugar-preferential uptake by tumor cells [3]. Tumor cells perform glycolysis at a faster rate than their noncancerous tissue counterparts, so increasing the glucose consumption with respect to healthy cells

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• -anomeric selectivity (Table 1). Noteworthy, the reaction also gave disaccharide 3n and 3o smoothly with complete α-anomeric selectivity albeit in a moderate yield. Likewise, reaction using Et3SiH gave the desired 2,3-unsaturated sugar 3i in 74% yield. These results testify to the robustness of the

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• Conjugation of steroids to carbohydrates and peptides The conjugation of steroids to other biomolecules such as carbohydrates and peptides represents a valuable strategy for providing new properties to the hydrophobic steroid skeleton. Naturally occurring steroid–sugar conjugates such as saponins have shown

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• ) – derived from a renewable resource like sugar cane biomass – for the incorporation of chiral pyrrolidine-based motifs capable to catalyze relevant asymmetric reactions. The incorporation of an organocatalyst into a polymer support requires either conjugation to the polymer or functionalization with a

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• between the equatorial sugar hydroxy groups and the receptor NH residues and also in the CH···π interactions with the hydrophobic anthrylene sidewalls. This combination of noncovalent interactions closely mimics the sugar-binding behavior exhibited by lectin proteins. The Davis group has explored more

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• addition of thiols to alkenes – known as thiol–ene coupling, TEC – a very efficient metal-free click reaction [18][19]. We prepared n-alkyl 1-thio-β--glycosides from unprotected sugar anomeric thiols, commercial n-alkenes and one synthetic lipophilic scaffold presenting two reactive alkenyl ends. Although

• with high affinity to lectins and with antibiotic activities [34], lectin recognition by n-alkyl thioglycoside liposomes remains unprecedented [33][34]. Moreover, the calculated distance between the two sugar moieties of compound 8 (up to 13 Å, Figure 6) and the presence of flexible arms make these

• compounds similar to other efficient multivalent glycoconjugates obtained by TEC of sugar thiols with different multivalent scaffolds such as octasilsesquioxanes [35], cyclopeptides [36][37] and polymers [38]. Both compounds 5 and 8 showed low IC50 values (a tenth to some hundreds of micromolars) where the

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• bidirectional macrocycles with exocyclic substituents with side chains derived from natural products [47]. The combination of acid components with side chains derived from natural products containing amino acid residues (e.g., Arg, Cys, His, Trp) and sugar, bifunctional components (diamino/diisocyanide) and

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• loads has led to mechanoenzymatic transformations [5][6][7], and to synthesize amino acid derivatives [8][9][10] and peptides [11][12][13] by ball milling and extrusion techniques. Similarly, mechanochemical derivatizations of sugars and sugar derivatives such as cyclodextrins (CDs) have proven

Influence of per-O-sulfation upon the conformational behaviour of common furanosides

• Alexey G. Gerbst,
• Vadim B. Krylov,
• Dmitry A. Argunov,
• Maksim I. Petruk,
• Arsenii S. Solovev,
• Andrey S. Dmitrenok and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2019, 15, 685–694, doi:10.3762/bjoc.15.63

• : O4–C1–O1–CH2 torsion was set to +60° or −60° depending on α- or β-configuration of the sugar in accordance with the exo-anomeric effect. Other starting torsions in the propyl group had trans-orientation. Geometry optimizations of all the thus obtained structures were carried out at ab initio HF/6-311

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• evade and suppress host immune responses [5][12][13][14][15]. The most prominent of these cell surface glycoconjugates, lipophosphoglycan (LPG), consists of a glycosylphosphatidylinositol (GPI) anchor and variable sugar capping structures (Figure 1) [15][16][17][18][19][20]. The capping sugar tropisms

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

• and their suitability for MGE. Three mannosamine derivatives in which the cyclopropene moiety is attached to the sugar by either an amide or a carbamate linkage and that differ by the presence or absence of a stabilizing methyl group at the double bond have been examined. We determined their DAinv

• , are not comparable. Additionally, the influence of the sugar derivative on the reaction rate has not been taken into account. Ac4ManNCyoc as well as Ac4ManNCp were shown to give after MGE a better membrane staining than Ac4ManNCyc [25][27]. A direct comparison of Ac4ManNCyoc and Ac4ManNCp in one

• acceptance of the Cp-modified sugar inspired us to develop novel derivatives of glucosamine and galactosamine containing this cyclopropene modification and to explore their behavior in MGE both for membrane-bound and intracellular glycoproteins. Results and Discussion Kinetic studies The second-order rate

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• pentasaccharide may provide ready availability of an amino functionality to expedite the conjugation of the pentasaccharide with an appropriate protein without affecting the sugar rings in the molecule [12][13]. Results and Discussion The target pentasaccharide as its 2-aminoethyl glycoside 1 was synthesized

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

• applicability, while most interesting developments in terms of synthetic efficiency, improved stereoselectivity and overall yields relate to the first approach. This approach, the synthetic glycosylation conditions depend on the nature of the sugar component. These conditions differ whether 1-halo-2,3,5-tri-O

• riboside. The stereochemical outcomes of the synthesis (anomeric ratio) depends on the nature and the stereochemistry of the leaving group X in sugar B (α- or β-anomer), on the nature of the substituents at the amide nitrogen atom in Nam, and on the conditions of glycosylation, such as solvent and

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• ]. There are also reports on the preparation of ‘distorted’ cyclodextrins in which diverse fragments are incorporated into the original oligosaccharide ring(s) [5]. Another class of sugar receptors is represented by macrocyclic derivatives with the carbohydrate unit being a part of a crown or aza-crown

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• crucial to determine structure–activity relationships and elucidate the particular sugar sequences involved in the interactions between CS and target proteins that regulate these biological functions. For this reason, several approaches have been reported for the synthesis of these molecules [2][3][4][5

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• conducted. This experiment revealed that the oligonucleotide containing five modified units was able to elicit the RNase H-mediated cleavage of the complementary RNA strand. Keywords: DNA/RNA affinity; fluorinated cyclopropanes; fluorinated nucleic acids; RNase H activity; sugar modified nucleosides

• oligonucleotides (AONs) [6]. An effective way to tune the properties of antisense oligonucleotides is by the insertion of the fluorine atom in the sugar moiety of the nucleoside. In this way, the sugar pucker can be controlled which ideally results in an increased affinity towards complementary RNA [7]. An

• improved affinity for RNA as complement can be found in DNA oligonucleotides containing 2’-deoxy-2’-fluoro-RNA (F-RNA) [8] or 2’-deoxy-2’-fluoroarabino nucleic acid (F-ANA, Figure 1) [9]. In the former the sugar pucker adopts a C3’-endo conformation [10] and the duplex formation is entropically stabilized

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• bacterial agglutination have provided initial insights into carbohydrate specificity, sub-cellular location and functions of putative mycobacterial lectins. In the thesis of K. Kolbe various sugar derivatives were immobilized in 96 well microtiter plates via an amino group. Bacterial adhesion was studied

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

• unsaturated 6’-fluoro[4.3.0]bicyclo nucleotides (6’F-bc4,3-DNA). Two 6’F-bc4,3 phosphoramidite building blocks (T and C) were synthesized starting from a previously described [3.3.0]bicyclic sugar. The conversion of this sugar to a gem-difluorinated tricyclic intermediate via difluorocarbene addition followed

• modification might be a substrate for RNase H. Keywords: DNA/RNA affinity; fluorinated cyclopropanes; fluorinated nucleic acids; molecular dynamics simulations; sugar modified nucleosides; Introduction A powerful strategy for the treatment of various disorders like cancer, viral and inherited diseases is the

• , Figure 1) [23]. Another strategy to overcome some of the limitations deals with the insertion of one or several fluorine atom(s) in the sugar moiety of the nucleic acid analog. The polar hydrophobic nature [24] of the fluorine atom can positively alter the furanose conformation, basicity and/or

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• was developed based on a Stille coupling to install the C-linked sugar residue [3]. Moreover, the addition of lithiated glycals to quinone derivatives followed by a rearrangement was also studied for the synthesis of kidamycin according to a “reverse polarity” strategy [4][5]. Considering that the

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• -acetylglycals [31][32] or other sugar-derived alkenes [33]. We first tried the conditions described in the literature (0 °C, mixture of methanol and dimethylformamide as a solvent), without much success in our case. Quite a few trials followed, changing the solvent to a dichloromethane/dimethylformamide mixture

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• sugar [41][42][43] and none for the synthesis of the α-D-GalpNAc-(1-3)-D-GalpNAc motif or its precursors. We therefore set out to study this regioselective glycosylation in more detail and synthesized the necessary model donors and acceptors. Here, the simplicity of the approach showed its potential, as

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• functionalized at the 5-position of the nucleobase with octadiynyl side chains and with azido groups at the 5’-position of the sugar moieties were synthesized. The macrocycles display freely accessible Watson–Crick recognition sites. The conformation of the 16-membered macrocycle was deduced from X-ray analysis

• and 1H,1H-NMR coupling constants. The sugar conformation (N vs S) was different in solution as compared to the solid state. Keywords: click cyclization; conformation; macrocycles; nucleosides; X-ray; Introduction The field of macrocycles was initiated by the work of Ruzicka and his structure

• . Monomeric purine and pyrimidine nucleosides form smaller ring systems known as cyclonucleosides incorporating O, N or S-bridges within the sugar moiety or between the nucleobase and the sugar residue [6]. Macrocycles can be obtained by a variety of chemical reactions [7][8][9][10]. Often, several protection

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• macrolide compounds, such as modification of the macrolide and the branched chain glycosyl residue, and replacement of the sugar group, are in the limelight [16][17]. The unique macrolide structure of spinosyns and the efficient appearance of resistance in some insect pests have prompted further exploration

• of spinosyns via chemical modification [18]. Bioactivities of many microbial secondary metabolites are highly dependent on their sugar constituents which are transferred as nucleotide-activated sugars to an aglycon by glycosyltransferases [19]. Therefore, bioactivities of these metabolites could

• change when the sugar constituents are altered. Previous studies have shown that modification of the spinosyn structure could potentially improve insecticidal activity and expand the insect spectrum [20][21]. Indeed, a large number of researchers have altered spinosad, replacing rhamnose or D-forosamine