Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• peptide–carbohydrate conjugation was achieved using tryptophan-containing peptides 29 and sugar-containing allyl carbonates 30 in chemo- and site-selective manners using a pyridyl directing group. The optimized reaction conditions entailed the use of dimanganese decacarbonyl as the catalyst and sodium

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• health and disease may affect multiple carbohydrate structures. Upon applying the Fisher’s exact test along with glycogene pathway classification, we identified TFs that may specifically regulate the biosynthesis of individual glycan types. Integration with Reactome DB knowledge provided an avenue to

• the addition of GlcNAc to processed N-linked glycan structures. These include all the MGAT enzymes. 7) GalNAc-type O-glycans: O-linked glycans are attached to serine (Ser) or threonine (Thr) on peptides, where GalNAc is the root carbohydrate. This is mediated by a family of about 20 Golgi-resident

• common core carbohydrate sequence attaching them to the corresponding proteins. These are constructed by the activity of specific xylotransferases (XYLT1 and XYLT2), galactosyltransferses B4GALT7 and B3GALT6 that sequentially add two galactose residues to xylose, and the glucuronyltransferase B3GAT3 that

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• the 1,3-diol motif [19]. The group is also associated with ease of deprotection, which is well documented in carbohydrate and sugar chemistry [20]. Comparison of our new route involving trityl and TBS protections with our previously published acetonide protection route for the synthesis of 4, showed

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• discussed herewith are constituted by furanosyl carbohydrate moiety. Nielsen and co-workers [67] synthesized the bicyclic double-headed nucleoside (1R,4R/S,5R,6R,8S)-8-hydroxy-1-hydroxymethyl-4,6-di(uracil-1-yl)-3,7-dioxabicyclo[3.2.1]octane (122), where the additional nucleobase is attached at the bridge

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

• . Keywords: amino sugars; deoxyfluorination; fluorinated carbohydrates; hexosamine hemiacetals; thioglycosides; Introduction Fluorinated carbohydrates are versatile carbohydrate mimetics used to probe or manipulate the recognition of carbohydrates by carbohydrate-binding proteins or carbohydrate-processing

• enzymes [1][2][3][4][5][6][7]. The introduction of additional fluorine atoms into a monofluorinated carbohydrate is an attractive way of modulating the binding affinity and pharmacokinetic properties of fluorinated glycomimetics. Hydrophobic segments incorporating multiple C–F bonds could (1) reduce the

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

• equilibrium. Keywords: fluorosulfite; glycosyl fluoride; Lewis acid; liquid sulfur dioxide; metal-free glycosylation; Introduction The glycosylation reaction is still one of the most important and basic synthetic strategies in carbohydrate chemistry that provides access to the various types of

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• biophysical, structural, and biological characterization of hexitol nucleic acids (HNA), mannitol nucleic acids (MNA), and altritol nucleic acids (AtNA) [216][217][218][219][220]. These carbohydrate-modified nucleosides incorporate a six-membered pyranose ring in place of the furanose ring found in unmodified

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

• Gangliosides are glycosphingolipids that contain a sialylated carbohydrate linked to ceramide. Typically located in the plasma membranes of many tissues, gangliosides are most concentrated in the brain, where they are the dominant feature of the neuronal glycocalyx [1][2][3]. The oligosaccharide is based on a

• . The method involves a set of regular-expression-based rules acting on strings of characters that representing the monosaccharide units, x, model the actions of transferases in the general form, Ax + B = A + xB, where Ax is a nucleotide sugar and B is the carbohydrate moiety of the acceptor, be it a

• the context. In this work, we consider only four monosaccharides and their corresponding letters: Glc (G), Gal (L), Neu5Ac (S) and GalNAc (V). In IUPAC form (see Table 1), we can write the carbohydrate portion of the ganglioside GM1a (Figure 1) as any of the following: Galb1-3GalNAcb1-4[Neu5Aca2-3

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• , France 10.3762/bjoc.17.30 Abstract Generally, carbohydrate-active enzymes are studied using chromogenic substrates that provide quick and easy color-based detection of enzyme-mediated hydrolysis. For feruloyl esterases, commercially available chromogenic ferulate derivatives are both costly and limited

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• [6][7][8][9] are only few of the numerous examples for multivalent protein–protein or protein–carbohydrate interactions that underline their pivotal role in biology. Mimicking polyvalency using synthetic systems has therefore become a growing field and the high degree of functionality renders

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• density functional theory (DFT) calculations). Finally, we wish to report the preparation of novel multi-vicinal fluorinated alditol analogues using a simple reduction protocol. Results and Discussion We initially supposed that DAST, a commonly used reagent to install fluorine atoms on the carbohydrate

• ). Interestingly, oxiranium ions in carbohydrate chemistry have been proposed as intermediates in the course of various reactions [20][29][35][36]. An equatorial fluorine atom at C2 (antiperiplanar to the C1–O5 bond) reduces the endocyclic oxygen polarizability, but also destabilizes a possible carbocation at C4

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

• Caparica, Portugal 10.3762/bjoc.16.229 Abstract In this paper we describe the synthesis of a new carbohydrate-based building block functionalized with azido or amino groups on the 2 and 4 positions. The building block can be synthesized in anomerically pure form in only five scalable steps starting from

• -consuming synthetic transformations employing costly reagents [15][16][17][18]. In this paper we describe the synthesis of a new carbohydrate-based building block that can be used for the synthesis of stimuli-responsive surfactants as it has the ability to be functionalized with both metal-chelating groups

• positions gave a compound with an on/off amphiphilicity as demonstrated visually. To conclude, the building block 5 gives access to a wide variety of functionalized derivatives and can be used for the synthesis of stimuli-responsive surfactants. a) The carbohydrate-based building block for the synthesis of

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• ]. It is a principle ubiquitously used in biology to achieve high affinity binding events with examples ranging from protein–carbohydrate interactions to host–pathogen interactions or cell surface adhesion [12][13][14]. The high affinity originates from the simultaneous interactions of multiple sites in

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• connects to the reducing end, Ha3. But if Ab3 was connected to the second Ha3 from right instead, we can specify the point of the cycle using a “c,” nGa6Ga4(-Ab3-)Ub2Ha3Hca3Ha3. Glycoconjugate rules describe when a reducing end of a SU is connected to non-carbohydrate moieties, Glycoconjugate rules

• complex carbohydrate is unknown. In reaction rules representation, “ * ” marks the “reaction site”, the position of the first difference between product and substrate strings in Linear Code form [7][10][13][32]. Note that the “reaction site” does not necessarily refer to the exact place that the reaction

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

• heterocyclic bases were studied in detail [16][17][18][19][20]. The transglycosylation reaction, that is the transfer of a carbohydrate fragment from a nucleoside donor to another heterocyclic base acceptor, was discovered by Kalckar in 1945 [16] (for reviews of pioneering works, see [17][18]). In a brief

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• initiatives have stored results in publicly available databases, some of which can be accessed through API interfaces. In the present work, we will describe how the Privateer carbohydrate structure validation software has been extended to harness results from glycomics projects, and its use to greatly improve

• and protein interactions [12]. Unfortunately, significant challenges have affected the determination of glycoprotein structures for decades and have had a detrimental impact on the quality and reliability of the produced models. Anomalies have been reported regarding carbohydrate nomenclature [13

• the lack of carbohydrate-specific modelling tools have often been named as the principal causes for these issues [18]. Heterogeneity of glycoproteins Unlike protein synthesis, which is encoded in the genome and follows a clear template, glycan biosynthesis is not template-directed. A single

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• glycobiologists or any researcher looking for a ready to use, simple program for the sketching or building of glycans. Keywords: bioinformatics; carbohydrate; glycan; glycobiology; nomenclature; oligosaccharide; polysaccharide; representation; structure; Introduction Glycoscience is a rapidly surfacing and

• information, coupled with the emergence of new platforms and technologies, has benefitted glycoscience to the point of enabling the detection and high-resolution determination and representation of complex glycans [1]. Increasing numbers of carbohydrate sequences have accumulated throughout extensive work in

• increases our understanding of biological processes. Representing the structures of carbohydrates has historically been considered to be a complicated task. Starting from the linear form of the Fischer projection, which is certainly not a realistic representation of a carbohydrate structure, there has been

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• -made analysis of over 1000 glycan array datasets from the CFG database (up to v5.1) via a web interface [48]. In this tool, rather than using predefined motifs, it utilizes Multiple Carbohydrate Alignment with Weights (MCAW) algorithm to align glycan structures as sequences based on their

• this software a user uploads a glycan binding protein complexed to a carbohydrate fragment in PDB format. This need not be a co-crystal structure, and can be a modeled structure as well. The application then finds glycans that contain this fragment which are present on the CFG microarray data and

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• -glycosylation; O-glycosylation; Python; Introduction Glycosylation is a key post-translational modification critical for protein folding and function in eukaryotes [1][2][3]. Diverse types of glycosylation are known, all involving modification of specific amino acid residues with complex carbohydrate

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• Micromonospora [5]. Dipeptide analogs with phosphonoproline 2 and piperidine-2-phosphonic acid 3 are potent inhibitors of dipeptidyl peptidase IV [6][7]. Oxygen-containing heterocycles containing a phosphoryl group are also of interest in the development of new drugs. It is known that phosphorylated carbohydrate

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• implicated in the cell’s interactions with its environment, facilitating communication and infection [1][2]. These processes are often initiated by molecular recognition involving carbohydrate-binding proteins (lectins) or by glycan–glycan interactions [1][3][4][5], all events that hinge on specific

• also of how specific modifications affect molecular recognition. Computational Methods All starting structures were generated with the GLYCAM Carbohydrate Builder (http://www.glycam.org). For each sequence we selected the complete set of torsion angle values obtained by variation of the 1-6 dihedrals

• , namely the three gg, gt and tg conformations for each 1-6 torsion. The topology file for each structure was obtained using tleap [31], with parameters from the GLYCAM06-j1 [32] for the carbohydrate atoms and with TIP3P for water molecules [33]. All calculations were run with the AMBER18 software package

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• . More importantly, we employed the 2-naphthylmethyl ether (Nap) group for protection of various hydroxy groups on the carbohydrate and acyl moieties, aiming to provide an advantage over previous methods that mainly used the benzyl group [4][14][15][16] in synthesizing lipid A derivatives. We also aim at

• reaction sequence of deprotection, acylation, phosphorylation, and global deprotection. The Nap protecting group has emerged as a particularly valuable addition to carbohydrate chemistry [24][25]. Not only does it not significantly alter carbohydrate reactivity, it also can be readily cleaved under

• hydrogenolytic conditions as well as a variety of oxidative [26] and acid-mediated conditions [25][27] that are orthogonal to benzyl ethers. Therefore, we employed the Nap ether as a “permanent” protecting group for the carbohydrate and the 3-hydroxy group of the acyl chain, aiming to provide an advantage over

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

• carbohydrate skeletons resembled the donor substrate: various RSO2 aglycons mimic an approaching acceptor substrate while the 1-O-phosphono moiety represents the leaving UDP [20]. The synthesis of target compounds 1–3 consisted of two different strategies. The first one was applied to a series of ᴅ

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• , ortho-C–H activation delivering the photoactive intermediate. Under visible-light irradiation, the SET process from the excited ruthenacycle to the haloalkane coupling partner leads to the formation of a stabilized alkyl radical (Figure 39). Next, radical attack at the para-position of the carbohydrate