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

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• medicinally active as well as smart functional materials possessing the pyrrole as a fundamental subunit [28][29][30]. Additionally, 3,4-disubstituted pyrrole derivatives are versatile building blocks for the production of diverse bioactive molecules like co-enzyme, alkaloids, porphyrins and other related

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

• ]. Also, the CCMV VLPs are resistant to enzyme degradation through the digestive tract [32][33][34]. It is to be kept in mind that possibly the shrimp’s virus, in contrast to CCMV VLP’s, needs specific receptors to be internalized in the shrimp cells. For these reasons, CCMV VLPs show quite an advantage

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

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

• -pong second (ketone amination, diol esterification, desymmetrisation in the second half reaction); ping-pong first (diol ester hydrolysis) and ping-pong both (prochiral diacids). For plausible values of enzyme kinetic parameters, the product enantiomeric excess (ee) can decline substantially as the

• reaction proceeds to high conversion. For example, an ee of 0.95 at the start of the reaction can decline to less than 0.5 at 95% of equilibrium conversion, but for different enzyme properties it will remain almost unchanged. For most mechanisms a single function of multiple enzyme rate constants (which

• study if and how the product ee declines at high conversion. Keywords: enantiomeric excess; enzyme; kinetic mechanisms; kinetic parameters; prochiral; Introduction There is great interest in using enzymatic catalysis in the synthesis of homochiral molecules. An early approach was to use

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

• 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

• O-linked glycosylation, with a web-based application, O-Glycologue, that allows knockouts of enzymes of O-linked glycosylation and the assignment of custom “wild type” sets of enzyme activities to study the effects of differential knockouts on the resultant networks [15]. In this article, we

• describe an extension of this method to gangliosides, and to the enzyme reactions associated with their biosynthesis. The formalism and the associated web application, now renamed Glycologue, provide a way to explore the effects of mutations that result in a loss of functionality, or promotion of disease

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• commonly used for the synthesis of biologically active compounds having enzyme inhibition and antiviral activity [1][2], and are found in the structures of many commercially available antidepressant drugs [3][4][5][6][7][8][9][10][11][12]. In addition, dibenzosuberenone (1) and polyconjugated derivatives

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

• increased in the presence of avibactam (4 mg/L) in all bacterial strains under observation. The MIC values of MER without avibactam were observed to be in the range of 2 mg/L to 4 mg/L, whereas after the addition of avibactam the antibacterial activity changed to <0.125 mg/L–1 mg/L, indicating the enzyme

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• diphenyldiazomethanes, available reagents carrying substituents on the phenyl rings. For example, covalent attachment of C60 to peptides is performed through a phenyl spacer, as it was demonstrated in a synthesis of fulleride 27 [89]. The latter compound was designed specifically for suppressing a HIV enzyme. The

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

• microwave irradiation, a mixture of monoacylated and diacylated products 3 and 4 in 52% and 33% yield, respectively, was isolated [28]. Enzymatic hydroxylation 3-Ketosteroid 9α-hydroxylase (KSH) from R. rhodochrous has been shown to oxidize C9 in several steroids [29]. This enzyme consists of two

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

• -volatile precursor that is stored in garlic and related plants and only degraded into sulfur volatiles upon wounding by the pyridoxal phosphate (PLP) dependent alliinase (Scheme 1B) [7]. This initial enzyme-catalyzed reaction yields one equivalent of allylsulfenic acid (10), pyruvic acid (11), and ammonia

• 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

• DmdABCD is fully established in P. inhibens, while genes for DmdD are missing in D. shibae and O. indolifex, suggesting that another enzyme with a low sequence homology may substitute for DmdD, leading to allylthiol and several sulfur volatiles derived from it in all three strains. The DMSP hydrolase DddD

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• and phosphonate-linked analogues of naturally occurring peptides. They are more stable than phosphonopeptides and have been widely applied as enzyme inhibitors, haptens for the production of antibodies, biological agents, and prodrugs. The synthetic strategies towards phosphonodepsipeptides are

• than the corresponding phosphonopeptides because the phosphonate bond is more inert than a phopshonamidate bond. Phosphonodepsipeptides are widely used as enzyme inhibitors [6][7][8][9][10], haptens for inducing catalytic antibodies [11][12], and produgs [8][9][13]. They have potential applications as

• -diazoalkylphononates can be readily prepared from the corresponding 1-aminoalkylphosphonates via nitrosation with amyl nitrite. Conclusion Phosphonodepsipeptides are phosphorus analogues of depsipeptides. They are more stable than the corresponding phosphonopeptides and have been widely used as enzyme inhibitors

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

• hydroxylating enzyme in E. coli has been previously achieved [36][37]. Bacterial prolyl hydroxylases have been characterized, and they are able to oxidize proline and analogous structures in recombinantly expressed proteins [38]. Nonetheless, we are still missing evidences of natural posttranslational

• example, the volume difference between Pro and Dfp is smaller than the difference between Val and Ile. It is therefore not surprising that Flp and Dfp can in principle be recognized as proline by natural enzyme binding pockets. The successful experimental incorporation of fluoroprolines into proteins

• based on the recognition of fluoroprolines by the native enzyme aminoacyl-tRNA synthetase (vide infra) proves this assumption. 2.2 Local polarity Another important feature of fluoroprolines is their local electrostatic potential (local polarity). In proline, position 4 contains a positive surface

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• TFMK moiety is a proven effective metal chelator in various enzyme inhibitors (Figure 1b) [58][59][60][61][62][63][64][65]. Several useful methods exist for preparing trifluoromethyl ketones [66][67], such as the direct trifluoromethylation of esters by the Ruppert–Prakash reagent (Me3SiCF3) [68][69

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• was sought. The possibility to exploit the use of an enzyme to derivatize benzyl alcohol into an easily separable species was an intriguing opportunity. To integrate such a biocatalyzed transformation into the continuous Curtius rearrangement process, immobilized CALB, a robust hydrolase enzyme was

• immobilized CALB enzyme is reported. This approach enabled the chemoselective derivatization of benzyl alcohol into the readily removable benzyl butyrate thus simplifying the final purification stages. The resulting Cbz-carbamates were furthermore elaborated into derivatives of β-amino acids via biphasic flow

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• 78 was incubated in the presence of IPP and the enzyme prenyltransferase, a rate of 5.1 × 10−4 nmol⋅min−1⋅mg−1 was measured for the condensation reaction (Scheme 24), which is to be compared to a value of 7.4 × 102 nmol⋅min−1⋅mg−1 observed for the condensation involving IPP and geranyl pyrophosphate

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

• ; hydrolysis; lipase; transesterification; Introduction The development of “white biotechnology” is underpinned by advances in enzyme discovery and engineering, areas that are being driven by metagenomics and in vitro-directed enzyme evolution. These techniques procure massive discovery or the creation of new

• enzyme-encoding sequences, filling up databases with a wealth of information. However, while resolving an early step in the discovery pipeline, these techniques progressively create a new bottleneck regarding enzyme characterization. Therefore, there is a pressing need to extend the enzymologist’s

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

• the γ-butyrobetaine hydroxylase enzyme (hBBOX) (Figure 5a–c). As the fluorine shift of the metabolised product is distinctively different from the shift of the precursor, by producing a novel fluoromethyl analogue of the γ-butyrobetaine substrate (GBBNF) Rydzik et al. were able to monitor carnitine

• biosynthesis through hBBOX-catalysed GBBNF hydroxylation, both in vitro and in cell lysates [43]. Moreover, by using a competitive substrate for the enzyme, inhibition experiments could be directly employed to determine the IC50 values in the basis of fluoride release, and the extent of GBBNF turnover

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• enantioselective functional group interconversions on prochiral or racemic difluorocyclopropane and difluorocyclopropene derivatives have provided important ways of obtaining enantiomerically pure cyclopropanes. The key reactions in this context are the enzyme-catalyzed formation and hydrolysis of esters and the

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• also discussed. Keywords: host–guest chemistry; macrocycles; noncovalent interactions; supramolecular photocatalysis; Introduction Enzyme-catalyzed reactions are often carried out fantastically in nature via noncovalent interactions of a substrate [1][2]. Inspired by these natural processes, chemists

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• complexes, with most of the complexes being homooligomeric complexes [58]. In fact, an analysis done in the BRENDA enzyme database [59] shows that there are more homooligomeric complexes than expected [60]. PPIs in homooligomeric complexes are usually difficult to predict using computational measures

Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

• Heiko T. Kiesewalter,
• Carlos N. Lozano-Andrade,
• Mikael L. Strube and
• Ákos T. Kovács

Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248

• , enzyme inhibition, or disruption of bacterial protein synthesis. This knowledge was primarily acquired in vitro when B. subtilis was competing with other microbial monocultures. However, our understanding of the true ecological role of these small molecules is limited. In this study, we have established

• Bacillus spp. produce various SMs [33][34]. The most prominent and bioactive SMs are nonribosomal peptides (NRPs), of which isoforms belong to the families of surfactins, fengycins, or iturins [35][36] (Figure 1). They are biosynthesised by large enzyme complexes, nonribosomal peptide synthetases (NRPSs

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• biological applications. Review Nucleoside triphosphates detection Nucleoside triphosphates play crucial roles in several biological processes including energy transduction, cellular respiration, enzyme catalysis, and signaling [35][36][37][38]. They are the most targeted anionic species because of their

• serine protease of human mast cells and is known to be involved in the pathogenesis of asthma and other allergic and inflammatory disorders [48][49][50]. The structure of the enzyme is tetramer, composed of four identical subunits arranged in two different orientations, around a central pore. In vivo

• heparin stabilizes the tetrameric structure, without its tryptase dissociates into inactive monomers. The reported cationic ligand binds at the rim of anionic residues around the entrance of the central pore, blocks the access to the active sites, and inhibits enzyme activity. Schmuck et al. reported a

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• cellular environment. Keywords: acetylation; branched peptides; enzyme; nanostructures; N-terminal; responsive; self-assembly; Introduction Peptides, being able to self-assemble to exhibit emergent properties and functions [1][2][3][4][5], have received considerable attentions recently. For example

• in a polymeric hydrogel for a responsiveness to thermolysin [35]. Dong et al. reported the branching of an oligopeptide via a cysteine linkage to result in multivalence [37]. During our studies on enzyme-instructed self-assembly (EISA) [38][39][40] of branched peptides for hydrogelation [32], we

• serendipitously found that an enzyme-responsive branched peptide was able to deliver small molecules or proteins to mitochondria efficiently in a cell-specific manner [33]. The branched peptide, which bears FLAG-tag as the branch [32], forms micelles. Certain proteases on the mitochondria of certain cells cleave

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• to different levels of flexibility within the enzyme active sites. A third possibility is that the analog 2 adopts different conformations upon binding to AChE vs BACE-1, since the microenvironments within the enzymes’ active sites could be different (e.g., more/less polar), the “correct” binding

• geometry of 2 might be favoured in AChE but not in BACE-1. These possibilities all remain speculative in the absence of high-resolution structural data of the enzyme–ligand complexes. Conclusion A threo-difluorinated piperine analog (2) was successfully synthesised through a stepwise route. The