Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• opening attempt of chiral oxirane 153 in the presence of BF3.Et2O (Scheme 20) [104]. The synthetic route to the desired product was smoothly brought to its course by employing CuCN in the medium. Amines The enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are responsible

• for tryptophan metabolism in the human body. Thus, the inhibition of these enzymes may help in tumor immunotherapy [105][106][107]. Xu recently found indole-2-carboxylic acid derivatives as IDO1/TDO dual inhibitors. In their effort to synthesize the following bis(indol-4-yl)amine derivatives via a

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• polysaccharides. For each class of polysaccharides, we discuss the available synthetic approaches and their current limitations. Keywords: enzymes; glycans; polysaccharides; synthesis; well-defined polymers; Introduction Polysaccharides are an abundant class of natural polymers that play important roles in the

• polymerization [18], C) chemical synthesis. The use of enzymes has undeniable advantages because it offers the possibility to use unprotected sugars as substrates and guarantees remarkable control of the regio- and stereoselectivity during glycosylation. Mono- or oligosaccharides bearing a reactive leaving group

• (LG, e.g., phosphate, fluoride, nucleotide) are polymerized by the enzyme to form the desired polysaccharide (Figure 1A). Several classes of enzymes are available, including hydrolases, phosphorylases, sucrases, glycosyltransferases, and glycosynthases [19][20][21][22]. An excellent overview of the

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• direct access to several sulfur-containing pharmacological compounds that present valuable biological activities, such as anti-HIV (9) [51], inhibition of snake venom enzymes (10) [52], or even anti-estrogenic effects (11) [53] (Scheme 4A). Recently, Hou and co-workers also explored the utility of a

• in good yields (Scheme 39C). The authors used the same methodology to synthesize two 4H-benzo[d][1,3]oxazin-4-one derivatives that act as inhibitors of two enzymes (compounds 130 and 131 in Scheme 39D). The first one is the enzyme C1r serine protease, involved in both inflammation and renal scarring

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

• to be constitutively active in luminal breast cancer and confers antiapoptotic characteristics to cells [21]. The other two communities detected consisted primarily of chromatin-modifying enzymes. Complex N-linked glycan synthesis and the dolichol pathway were significantly enriched in the second

• community. In the third community, O-linked mannose and LacdiNAc synthesis were disproportionately regulated. Overall, the pathway maps suggest that chromatin remodeling enzymes could potentially play roles in regulating glycan synthesis in luminal breast cancer. Like luminal, basal breast cancer TF

• –glycogene relationships were also clustered into three communities. Here, the first community was enriched for chromatin-modifying enzymes, with complex N-linked glycan synthesis being the primary glycosylation pathway being affected (Figure 5a). The second community was enriched for interferon α/β/γ

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• precursors GPP, FPP, and GGPP into the different terpene skeletons [42][43][44]. However, our knowledge on terpene synthases of endophytic fungi is scarce, specifically in comparison to the vast knowledge on these enzymes in plants and bacteria [44][45]. Typical monoterpenes like limonene and linalool (5

• respective enzymes accepted the substrate GPP and produced monoterpenes (Figure 2). CxTPS1 produced myrcene (9) and (E)-β-ocimene (10) in similar amounts. CxTPS2 produced (E)-β-ocimene (10) as the major product and minor amounts of myrcene (9), (Z)-β-ocimene (11), and linalool (5) (Figure 2). Only one

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

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• lost in the water by pellet detachment; 2) were not ingested by shrimp; 3) shrimp enzymes degraded it; or 4) a high concentration of VLPs was lost in feces. We hypothesized that an adequate amount is not being absorbed, since the observed survival rate does not exceed 50%. Thus, the problem is not the

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• aspartokinase (ask_ect). Aspartokinase (Ask), along with ʟ-aspartate-β-semialdehyde-dehydrogenase (Asd), provides the precursor ʟ-ASA for ectoine biosynthesis [33][44][45]. Homologs of the enzymes of the ectoine pathway from Halorhodospira halochloris were identified by BLAST searches of the U. mutabilis genome

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• . Other examples of the use of column reactors for the catalysis of aldol reactions include: The use of immobilised aldolase enzymes for the synthesis of carbohydrates [114] and the use of a calcinated hydrolactite-packed column for the condensation of furfural with acetone [115], however, this still

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

• 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

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

• production of proteins, enzymes and receptors that may be inhibited by small-molecule and antibody therapeutics. However, native RNA oligonucleotides do not possess sufficient metabolic stability for in vivo applications. Therefore, chemical modification is absolutely essential to re-engineer RNA into a

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• enantioselective enzymes in the resolution of a racemate. As such resolution reactions proceed, there are progressive changes in the enantiomeric excesses (ee), that of the product falling while that of the residual starting material increases. In a classic study of the kinetics of resolution, Chen and Sih [1

• medium). It would thus be possible to treat all but 2 of the rate constants as independent input parameters. However, this is not the most sensible approach. Instead, combinations of rate constants can be related to values more likely to be known by users of relevant enzymes. And other combinations prove

• overall picture. A further criterion was a preference for dimensionless parameters, like the ratio of two elementary rate constants (both first order or both second order). Dimensionless parameters make it easier to represent all possible behaviour of diverse enzymes. Finally, many parameters could be

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• therapeutic strategy [2][3][4][5]. Antigene strategies use ONs to specifically bind native DNA, induce genomic changes, and/or interfere with gene expression. Apart from strategies that use modular enzymes such as zinc-finger nucleases [6] or transcription activator-like effector nucleases (TALENs) [7] to

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

• those of the central nervous system, where they function in intercellular recognition and communication. We describe an in silico method for determining the metabolic pathways leading to the most common gangliosides, based on the known enzymes of their biosynthesis. A network of 41 glycolipids is

• produced by the actions of the 10 enzymes included in the model. The different ganglioside nomenclature systems in common use are compared and a systematic variant of the widely used Svennerholm nomenclature is described. Knockouts of specific enzyme activities are used to simulate congenital defects in

• gangliosides, such as GD1α, promote tumor-cell adhesion during metastasis [13]. The cholinergic neuron-specific gangliosides GQ1bα and GT1aα may contribute to the pathogenesis of Alzheimer’s disease [14]. Previously, we described a deductive apparatus of a formal system for modelling the enzymes of mucin-type

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• , sulbactam and tazobactam [13] evolved as the BLIs of class A, B and few of class D β-lactamases [14]. These inhibitors were advantageous to clavulanic acid due to their lack of chromosomal induction of AmpC but found susceptible to a few of class A enzymes such as TEM type [10] and CTX-M (ESBL), identified

• amidines at the C2 position of DBO in moderate to good overall yields. In vitro antibacterial testing of the compounds was performed against ten bacterial strains containing different β-lactamase enzymes. The compounds were tested alone and in combination with the existing antibiotic, meropenem. All

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• review. Biological catalysts for the deconstruction of plastics were extensively studied in the past years, and several hydrolytic-enzymes-containing microorganisms have been shown to be usable for this purpose [112][113]. However, enzymatic depolymerisation is hampered by high molecular weight and

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• cellular lysate of the marine gorgonian Pseudopterogorgia americana was published by Keliman et al. in 1996 [26]. They carried out quite effective transformations of a variety of sterols to 9,11-secosteroid derivatives in high yields. However, it is unclear which enzymes were responsible for each oxidation

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• compounds, structural suggestions were made based on their mass spectrometric fragmentation pattern and confirmed by the synthesis of reference compounds. The results of the feeding experiments allowed to conclude on the substrate tolerance of DMSP degrading enzymes in marine bacteria. Keywords: Allium

• giving another example for the complex interactions between marine bacteria and algae. Known DMSP degradation pathways include its hydrolysis to dimethyl sulfide (DMS) and 3-hydroxypropanoic acid (15) by the enzyme DddD [19], or the lysis to DMS and acrylic acid (16) for which various enzymes including

• ), allyl methyl trisulfide (32), and traces of diallyl trisulfide (3) and allyl methyl tetrasulfide (34) were observed. The formation of these compounds is explainable by the deallylation of DAllSP to 3-(allylsulfanyl)propanoic acid (37) and further degradation to allyl thiol (13) through the enzymes of

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• , Mn and mainly Co-based catalysts for olefin epoxidation. Besides their low cost and low toxicity, the choice of these metals is related to their known ability to activate dioxygen in natural processes catalyzed by metal-containing enzymes [29][30]. Despite that various homogeneous [31][32] and

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• the velocity as well. For example, in the nonpolar environment of a protein interior or a hydrophobic pocket of a chaperone, the process may occur much faster [53]. Some protein sequences require the action of peptidyl-prolyl cis/trans isomerases, natural enzymes meant to facilitate the amide rotation

• S-Flp may preclude the production of proteins with this substrate as the in vivo expression of enzymes with oligoproline stretches might be completely suppressed with this analogue (vide infra). Chin and co-workers reported the directed evolution on ribosomes that yielded a variant (dubbed as O-d2d8

• incorporation on the enzymatic performance were characterized for a few enzymes [59][130][131][132][135] and the activity of ion channels [110][111][112][113]. These studies generally showed the preservation of the fold of the parent enzymes inferred from the preservation of their native activities. From these

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• demethylation pathway by action of the enzymes DmdABCD to methanethiol (MeSH, Scheme 1A) [12] or through lysis by DddD [13] or hydrolytic cleavage by one of the known DMSP lyases (DddW [14], DddP [15], DddQ [16], DddL [17], DddY [18] or DddK [19]) to dimethyl sulfide (DMS, Scheme 1B). It has already been

• , for which all relevant enzymes are encoded in the six Celeribacter strains (only a DmdA homolog is missing in C. indicus, Table S1 in Supporting Information File 1), and e.g., transesterification of the DmdC product with EtOH (Scheme 1A). Compound 42 is not a widespread sulfur volatile, but has been

• possibilities for future studies on methionine and DMSP degrading enzymes and pathways in Celeribacter. Our study also shows that the results from trace compound analyses must be taken with care and contaminations from other sources must always be taken into consideration. For the unusual compound 2

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

• toolbox, providing informationally rich high-throughput screens that can not only attribute an activity to putative enzymes but also procure some qualitative details on enzyme properties. In this respect, the availability of easy-to-use chromogenic substrates that can provide both qualitative and

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• and complex biomolecules, such as enzymes. In a recent study exemplifying this application, 19F NMR has been employed to investigate the metabolism of carnitine. In animals, carnitine is biosynthesised from trimethyllysine in four enzyme-catalysed steps, which involves in the last step the action of

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• provides a powerful workflow towards high-throughput glycopeptide analysis. Experimental Sample, chemicals, and enzymes Human plasma Visucon-F was obtained from Affinity Biologicals (Ancaster, ON, Canada). Affinity matrix beads for IgG (CaptureSelect FcXL, capacity 25–35 g/L) and IgA (CaptureSelect IgA

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• antibiotic, is used for the treatment of resistant bacterial infections. Its interaction with a small peptidic segment of the bacteria cell wall is a classic example of molecular recognition [6][7]. Peptides are often substrates for protease enzymes [8][9]. Enzymologists have studied the chemical principles