Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• of dIno) in 10 mM Na-phosphate buffer (pH 7.4) at 22 °C for 6 h. Noteworthy, the formation of the 2'd-N7- and 2'd-N9-glycosides of N2-acetylguanine (AcGua) was observed in the transglycosylation of AcGua using dGuo/E. coli PNP (67.5 IU per 1 mmol base) for an in situ generation of dRib-1Pi (5 mM K

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• range of biomolecules: amino acids [8], peptides [9], glycosides [10], nucleosides/nucleotides [11], and lipids [12]. Also, protein-based nano-bio-conjugates [13] have been prepared by ball milling, retaining the native properties of the proteins after mechanochemical synthesis. Boronic acids and their

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• method, an enyne precursor was first converted into an exocyclic 1,3-diene in 92% yield. A Diels–Alder reaction with naphthoquinone and a deprotection step then led to the final compound (−)-zenkequinone B in a stereoselective manner (Scheme 23). C-Aryl glycosides Another interesting report from

• Kaliappan et al. [93] described a highly efficient synthesis of C-aryl glycosides, which are naturally occurring compounds of biological relevance. Starting from a glycoside precursor, the intermolecular enyne metathesis with ethylene gas in the presence of the second-generation Grubbs catalyst allowed the

• ). Subsequent Diels–Alder cycloaddition reactions with dienophiles and further aromatization reactions paved the way for a convenient access to structurally diverse polycyclic compounds. For instance, installing the C-aryl and spiro-C-aryl glycosides in the same moiety was successfully achieved. An application

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• , followed by iodination and phosphonate introduction by an Arbusov reaction. Alternative approaches were elaborated from olefinic C-glycosides, which were converted into the corresponding C-linked hydroxymethyl derivatives and processed to give the glycosyl methylphosphonic acid derivatives [18][19]. As the

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

• order to allow for anomerization to occur (Scheme 1) [20]. In our hands, treatment of methyl glycosides 7 and 8 with two equivalents of protecting reagents resulted in the formation of a mixture of di- and trisubstituted derivatives, and thus the regioselectivity could not be controlled. All Galp

• acceptors were prepared from the corresponding isopropylidene derivatives 9α or 9β. For their preparation, methyl glycosides 7 or 8 were treated with 2,2-dimethoxypropane and catalytic amounts of p-toluenesulfonic acid, followed by a mild treatment with TFA to hydrolyze the formed byproducts, such as open

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• manipulations on the commercially available monosaccharides and stereoselective chemical glycosylations. The 2-aminoethyl glycoside at the reducing end will facilitate further glycoconjugate formation without hampering the stereochemistry of the anomeric center. We have used similar glycosides in case of other

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

• a powerful synthetic tool for the efficient and diastereoselective elongation of melibiose (1) without affecting the existing glycosidic linkage, allowing for additional options for further modifications of complex glycosides. Experimental 2’,3’,4’,6’-Tetra-O-acetyl-α-ᴅ-galactopyranosyl-(1’→1

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

• developed for the synthesis of 2,3-unsaturated C-, O-, N- and S-linked glycosides (enosides) using 20 mol % perflurophenylboronic acid catalyst via Ferrier rearrangement. Using this protocol, D-glucals and L-rhamnals reacted with various C-, O-, N- and S-nucleophiles to give a wide range of glycosides in up

• to 98% yields with mainly α-anomeric selectivity. The perflurophenylboronic acid successfully catalyzed a wide range of substrates (both glucals and nucleophiles) under very mild reaction conditions. Keywords: C-; O-; N- and S-linked glycosides; enosides; Ferrier-rearrangement; organocatalyst

• ; pseudo-glycosides; Introduction 2,3-Unsaturated glycosides, also known as pseudo-glycosides or enosides, are an important class of natural products with many biological activities and capacity to serve as substrates for further reactions [1][2][3]. They are involved in biochemical processes such as

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

• and complexity-generating processes [2][3] have proven success in peptide ligation [4] and macrocyclization [5][6], protein glycoconjugation [7], lipidation of peptides [8] and glycosides [9], and carbohydrate modification [10]. A special class of lipidic biomolecules are the steroids, which can be

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

• -negative bacteria [7] are challenges for the current research in the field. Artificial OMV, composed of synthetic and non-toxic, non-immunogenic phospholipids and glycolipids are good candidates for drug or vaccine delivery. One of the most common reactions used to prepare monoalkyl glycosides is the

• ]. Some of them have been obtained by coupling protected glycosyl thiolates and n-alkyl halides [14][15][16]. Moreover, mechanochemical thioglycosylation of glycosyl acetates was used for the synthesis of n-alkyl 1-thio-α--glycosides as carbohydrate mesogens [17]. Unfortunately, the preparation of alkyl

• glycosides cannot be carried out with unprotected thio-glycosides, implying orthogonal protection and deprotection steps in order to obtain unprotected glycolipids. We decided to investigate the formation of artificial OMV composed of long chain alkyl thioglycosides synthesized by the photoinduced radical

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

• drastic changes of the ring conformation occurred while sometimes only the conformation of the exocyclic C4–C5 linkage changed. Herein we describe a combined quantum chemical and NMR conformational investigation of three common monosaccharide furanosides as their propyl glycosides: α-mannose, β-glucose

• analogous reactions (Scheme 1). The use of the n-propyl group as an aglycon allowed for efficient purification of the desired glycosides utilizing C18 reversed-phase chromatography. Galactofuranoside 3 was previously synthesized using pyranoside-into-furanoside rearrangement [14]. The per-O-sulfation [24

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

• preparing acetobromo glycoses. In order to show the suitability of our flow system for the preparation of simple glycosides, we first tested Koenigs–Knorr glycosylation conditions with silver triflate as activator. Thus, silver triflate (2 equiv) was mixed with molecular sieves (4 Å) and placed in a packed

• glycosides 3–7 were obtained. To the best of our knowledge similar cascade flow glycosylations have not been described in the literature so far. Finally, the herein developed flow system devices could also be applied to the continuous flow preparation of glycosyl azides. For example, we were able to convert

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

• has already been studied and reviewed in detail [21][39], we focus this review on the rarely studied mycobacterial lectins and their roles in recognizing glycosides on the surfaces of host immune and epithelial cells. Review Glycosides on the surfaces of mycobacteria and their host cell Eukaryotic

• results are similar to previous observations with other lectins. Adhesion and inhibition studies with the fimbrial lectin FimH of E. coli bacteria, for example, also revealed higher affinities of glycosides carrying an aromatic aglycon compared to derivatives with aliphatic aglycon portions. This finding

• adhesion and uptake, as well as intracellular survival of the pathogen. The relevance of mycobacterial lectins for host–pathogen interactions has been poorly studied and is the focus of this review. Both mycobacteria and mammalian host cells possess unique subsets of glycosides on their cell surfaces. The

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• adhesion in mice [18][19]. These compounds have been extensively optimized in many works published by both groups, culminating in the identification of mannophosphates as prodrugs to increase oral bioavailability [20] and mannose C-glycosides, such as compound 6 , demonstrating enhanced in vivo metabolic

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

• achieve good results in the Mitsunobu procedure. We have reviewed on the one hand the literature on anomeric esterification, including glycosyl phosphates, and on the other hand glycoside synthesis, including S- and N-glycosides. The mechanistic details of the Mitsunobu reaction are discussed as well as

• to be either converted into glycosides or into other anomerically modified carbohydrate derivatives. We intend to provide a critical survey as well as a source of inspiration, even more so as glycosylation remains a challenge in carbohydrate chemistry. Review Mechanistic considerations Since

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

• -acyloxyglycoside 164 with good selectivity at the anomeric position as a consequence of participation by the neighboring C2 acyloxy group (Figure 8). They prepared C2-acyloxy glycosides 165, 166, 169, 170 and 172 using hypervalent iodine-mediated coupling reactions with glycals, and the results are shown in Scheme

• oxidative glycosylation reaction to stereoselectively give C2-acyloxylated β-glycosides in good yields [84] (Scheme 22). Hotha and co-workers utilized the reaction of glycals with hypervalent iodine reagents for the stereoselective synthesis of C2 deoxyglycosides and amino acid glycoconjugates [85]. In

• evaporation of a mixture of PhI(OAc)2 and amino acid 173 and 174 in chlorobenzene to give PhI(OCOR)2 compounds 175 and 176. The formation of iodo ester glycosides 178 and 179 from 175 and 176 was achieved in very good yields under the conditions shown in Scheme 23. Notably, the resulting iodo ester glycosides

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

• -alkynic glycosyl donors, glycosyl halides [18], armed O-methyl glycosides [19], armed and disarmed thioglycosides [20] as well as trichloroacetimidate [21][22] donors were successfully applied to O- and C-glycosylations. Of the gold-catalyzed N-glycosylation reactions, Yu et al. demonstrated the effective

• -glycosides are also accessible by AuCl3/phenylacetylene-promoted Ferrier rearrangement of glycals [17], thus, demonstrating the efficient catalysis by alkynophilic and carbophilic Au complexes. Although the alkynophilicity and carbophilicity of Au complexes are well explored, very little is known about the

• -glycosylation albeit in low yields, thus indicating the possible utility of the oxophilic character of Au(III) towards the acetylated sugars. Among the N-glycosides, anomeric azido glycosides are important intermediates due to various applications in the synthesis of various glycosyl amides [28][29

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• glycosides on mammalian cell surfaces. After this initial contact, they can infect host cells and form biofilms, both of which are key factors for their survival [9][27][28]. Examples of such opportunistic bacterial species binding to mannosides on host cells include Pseudomonas aeruginosa with its membrane

• to 1.7 nM for glycosylated gp120 (25 glycosylation sites) [43][77]. In the case of UPEC, each bacterium contains three to five hundred fimbriae to potentiate multivalency, as each FimHLD (I) at the fimbrial tip can interact with mammalian UPIa [78]. Multivalent glycosides have also been investigated

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

• thiourea derivative as an hydrogen-bonding cocatalyst. This transformation occurs under mild reaction conditions with a wide range of O-glycosyl trichloroacetimidate donors and glycosyl acceptors to afford the corresponding O-glycosides in moderate to good yields with predictable selectivity. In addition

• our own research interest in developing stereoselective glycosylation methods, we decided to focus our attention on the synthesis of glycosides via cooperative catalysis. A highly reactive glycosyl donor for instance, O-glycosyl trichloroacetimidate, generally requires a pKa value less than 5 for

• produced in 72% yield with moderate selectivity (Table 2, entry 13) and the acid sensitive group survived well [34]. To further demonstrate the efficacy of this method other important glycosides were synthesized with different donors as tabulated in Table 3. Glycosylation of D-galactopyranosyl

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

• the obtained compounds are active against Gram-positive bacteria and Candida type fungi. Keywords: antimicrobial activities; D-galactosamine; diosgenin; glycosylation; saponin; tetrachlorophthalimido derivatives; Introduction Saponins are steroid or triterpenoid glycosides found in various plants [1

• glycosides constitute a very important group among spirostanol saponins. Diosgenin has a double bond between the C-5 and C-6 atoms of the spirostanol skeleton and can be found in combination with different sugars in Costus, Discorea, Paris, Solanum, Yucca, and Trillium plants [11]. The plants containing

• tigogenin linked with D-galactose [16]. Moreover Smilacina atropurpureea, Solanum indicum, and the genus Yucca contain smilacinosides and funkiosides [17], indiosides [18], and elephanosides [19]. All these saponins are glycosides, where diosgenin is attached directly with D-galactose. Besides their

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• as sulfate esters and deoxy glycosides have been successfully synthesized. The preactivation-based chemoselective glycosylation is a powerful strategy for oligosaccharide assembly complementing the more traditional premixed method. Keywords: chemoselectivity; glycosides; preactivation; synthesis

• . Preactivation-based iterative glycosylation of 2-pyridyl glycosides O-Unprotected 2-pyridyl glycosyl donors have been utilized in oligosaccharide synthesis [29]. The Ye group reported a preactivation protocol using protected 2-pyridyl donors [30]. The preactivation of 2-pyridyl glycoside 14 was performed using

• anomeric reactivities of deoxy glycosides compared to the corresponding pyranosides. Upon the addition of the acceptor, the glycosyl chloride could be activated by AgOTf producing the glycosylation product with good α selectivity. To test the applicability to iterative synthesis, donor 143 was preactivated

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

• 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

• and yields. Hence, intramolecular glycosylations have a particular relevance to special cases of glycosylation or particularly challenging targets, such as 1,2-cis glycosides, where other, more direct methods fail to provide acceptable results. Presented herein is an overview of methods that have been

• introduced by Kusumoto et al. [46], however, this term was coined by the same group much later [51]. We adopt this term to generally refer to this concept, which in other applications was also named “intramolecular glycosylation of prearranged glycosides” by Ziegler [52][53], “template-directed cyclo

• tethers Ziegler and co-workers investigated the use of a flexible succinoyl linker to link the glycosyl donor and acceptor counterpart. This reaction was named “intramolecular glycosylation of prearranged glycosides” [52][53]. Like in all “molecular clamp” applications, the tethering of the reaction

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• procedures have been successfully applied to the synthesis of O-glycosides [10], bioactive hydantoins [11], extended iptycenes [12] and organometallics [13] where problems can occur using solution-based synthesis due to limited solubility. Whilst mechanochemical one-pot procedures offer the inherent ability

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

• thought to represent powerful and greener alternatives to conventional chemical glycosylation procedures. The knowledge of their corresponding mechanisms has already allowed the development of efficient biocatalysed syntheses of complex O-glycosides. These enzymes can also now be applied to the formation

• . Rational mutagenesis, directed evolution, or even de novo design have dramatically broaden the applicability of enzymes in biocatalysis [7]. In the glycochemistry field, a vast array of carbohydrate-metabolizing enzymes [8] has been used to synthesize glycosides, even using multiple enzymes systems

• pharmaceutics [11]. Classically, glycosides are linked to the aglycone moiety through an oxygen or a nitrogen atom, although many other kinds of linkages (even if rare) can be found in nature like in glycosylated proteins for example [12]. Herein, we wish to report a short but comprehensive review of the