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

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

• -glucosamine and the sugar was linked to the aromatic system via an annulated oxazoline. Palladium complexes of 2 were used in allylic substitution of allyl acetates with dimethyl malonate as nucleophile and ee values from 69% to 98% were obtained [19]. Recently, we presented the synthesis of carbohydrate

• pyridyloxazoline (PyOx) ligands in which the sugar moiety was linked to pyridine via an annulated oxazoline, 3, as well as via a spiro-fused oxazoline, 4. We found that the spiro-fused ligands gave higher enantioselectivities (up to 93% ee) than the annulated ligands (up to 66% ee) in allylic substitution [20][21

• phosphines. We chose Stoltz’s protocol to introduce the diphenylphosphine moiety to our β-configurated bromoaryloxazolines 10a–i as well as to oxazoline 11i due to the fact that the peracetylated sugar could be obtained as an α-anomer in relatively high yield. The reaction afforded the spiro-fused PHOX

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• RGO the esterification process is conducted with water as a reaction medium are also found in the literature [38][39][40]. For example [38], the formation of ester-type linkages have been found between the carboxyl group of GO and the hydroxy group of a sugar derivative via a water-based reaction

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• Information File 1 for side reactions), both the lipid 9 and the protected sugar 10 were also effectively conjugated to the activated 5’-terminus under the same reaction conditions to give the desired bioconjugates 11 and 12, respectively (Table 2, entries 3 and 4). We finally examined whether relatively

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• accuracy. We are concluding from this study that photolabeling of FimH with sugar diazirines has only very limited success and cannot be regarded a facile approach for covalent modification of FimH. Keywords: diazirines; docking; FimH; lectin ligands; mannosides; mass spectrometry; photoaffinity labelling

• . Finally, back in 2010, we analyzed photolabeling of the octapeptide angiotensin II with three different sugar diazirines using mass spectrometry and then also detected photolabeling of FimH with the same three mannosides. However, we could not measure the labeling product with full accuracy [11]. Although

• reasoned that high performance mass spectrometry-based proteomics could lead to more robust success in our approach to employ tailor-made sugar ligands for FimH labeling. Here, we report on the difficulties of FimH labeling even when computer-aided design and synthesis of photolabile FimH were combined

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• Shahien Shahsavari Chase McNamara Mark Sylvester Emily Bromley Savannah Joslin Bao-Yuan Lu Shiyue Fang Department of Chemistry, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA Nalco Champion, an Ecolab Company, 11177 S. Stadium Drive, Sugar Land, TX 77478, USA

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

• reagents, mostly triphenylphosphine and a dialkyl azodicarboxylate. This reaction has been frequently used in carbohydrate chemistry for the modification of sugar hydroxy groups. Modification at the anomeric position, leading mainly to anomeric esters or glycosides, is of particular importance in the

• glycosciences. Therefore, this review focuses on the use of the Mitsunobu reaction for modifications of sugar hemiacetals. Strikingly, unprotected sugars can often be converted regioselectively at the anomeric center, whereas in other cases, the other hydroxy groups in reducing sugars have to be protected to

• hand, the equilibrium between the azodicarboxylate, the phosphine, and the acidic component, Nu-OH, is important (cf. Scheme 2, left dashed box). On the other hand, mutarotation of the sugar hemiacetal has to be discussed to predict the stereochemical outcome of the reaction. Mutarotation results in an

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

• , Tokushima, 770-8505, Japan 10.3762/bjoc.14.137 Abstract To synthesize nucleoside and oligosaccharide derivatives, we often use a glycosylation reaction to form a glycoside bond. Coupling reactions between a nucleobase and a sugar donor in the former case, and the reaction between an acceptor and a sugar

• glycoside bond. In the case of nucleoside synthesis, a coupling reaction between a persilylated nucleobase and a sugar donor is typically used [15][16][17]. On the other hand, the reaction between an acceptor and sugar donor is carried out in the presence of an appropriate activator for oligosaccharide

• synthesis [18][19]. In both cases, a Lewis acid is generally used as an activator for sugar donors. Our previous review focused on the development of glycosylation reactions and their application to the synthesis of nucleoside derivatives [17]. In this review, we showed our glycosylation reactions under

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• drug conjugates. Dox has three potential conjugation sites; i) a primary OH group at C-14 on the aglycone part, which is suitable for ester bond formation, ii) an oxo group at C-13 is available for the generation of an oxime linkage and iii) the amino group on the daunosamine sugar moiety, which can be

• amide bond through the sugar moiety (glut) (2) in solution. Furthermore, an oxime linkage was formed between Dox and an aminooxyacetyl moiety connected to the enzymatically cleavable tetrapeptide spacer GFLG (3). These conjugates were prepared with the aim of comparing the influence of the homing

• fragmentation of the conjugate between the aglycon part and sugar moiety resulted in fragments in which the peptide was attached either the aglycon OH group or the amino group of sugar moiety [23]. When unprotected Dox was used for the reaction with glutaric anhydride, the amino group was modified with glutaric

Spectroelectrochemical studies on the effect of cations in the alkaline glycerol oxidation reaction over carbon nanotube-supported Pd nanoparticles

• Dennis Hiltrop,
• Steffen Cychy,
• Karina Elumeeva,
• Wolfgang Schuhmann and
• Martin Muhler

Beilstein J. Org. Chem. 2018, 14, 1428–1435, doi:10.3762/bjoc.14.120

• from starch, sugar or oils and fats [2][3]. The transesterification of oils and fats produces glycerol as a byproduct, which requires further processing to reduce the costs of biofuels [4]. The comparably high energy density of glycerol of 5965 Wh L−1 assuming its total oxidation to CO2 suggests its

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• charged moieties attached to nucleobases or the ribose sugar. Some selected examples 1–6 of resulting nucleic acid structures are provided in Figure 2 [30][31][32][33][34][35][36][37]. Oligonucleotides of this type are at least partially zwitterionic, but overall densely charged. With respect to the

• ' (Figure 5) [72][73][74]. In principle, the NAA-modification is inspired by 'high-carbon' nucleoside structures (i.e., nucleosides having more than five carbon atoms in the sugar unit) found in naturally occurring nucleoside antibiotics [75][76][77]. In muraymycin- and caprazamycin-type nucleoside

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• several ways such as helical sense, pitch, groove width, base orientation and sugar pucker (Table 1). The major differences in the two generally encountered A- and B-forms of DNA is in the sugar pucker and their groove widths. In A-form DNA, the major groove is narrower but has a wide/shallow minor groove

• -form DNA, Z-DNA is a left handed structure formed by alternating G and C base pairs and contains some features of both A- and B-DNA such as the sugar pucker and a slightly bigger number of base pairs per turn [7]. The discovery of multistranded DNA structures such as G-quadruplexes [9], which uses

• eight Hoogsteen-paired hydrogen bonds to form a tetrad (Figure 1) has further enhanced our understanding of the diversity of DNA shapes and structures. In a parallel tetramolecular quadruplex d(TG4T), the features of nucleotides at each base resemble that of the B-DNA (C2’-endo sugar pucker, anti

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• Reactions of nucleoside sugar and nucleobase moieties An early example of the application of mechanochemistry for nucleoside derivatisation was reported by Khalafi-Nezhad and Mokhtari who effected regioselective 5′-protection of ribonucleosides and thymidine using a mortar and pestle with trityl

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• sugar moiety. The difference between Dau and Dox is a hydroxy group substituted at the C-14 carbon atom on Dox providing an extra conjugation site for ester linkage (Figure 6). The mechanism of action of anthracyclines is based on their intercalation to DNA inhibiting the macromolecular biosynthesis

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• relationship studies. Several strategies for the synthesis of 2-amino sugars have been published so far. In one exemplary straightforward approach, GalNAc was prepared by inverting the stereogenic center at the C-4 position of N-acetylglucosamine (GlcNAc) [10]. However, the necessity of using a 2-amino sugar

• of the four desired stereogenic centers. By extending compound 5 via a Horner–Wadsworth–Emmons (HWE) reaction [15] and subsequent stereoselective introduction of the corresponding nitrogen functionality, a route to four different 2-amino sugar stereoisomers has been elaborated. Results and Discussion

• cleaved by the use of acidic ion exchange (DOWEX H+). Subsequent ozonolysis caused the formation of the aldehyde by the oxidation of the methylene functionality. Consequently, intramolecular hemiacetal formation resulted immediately in the cyclization of the unprotected azido sugar, which was