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

• vivo applications [163]. Inefficient and incomplete release from endosomes remains an unsolved problem for PNA–CPP conjugates [164]. In this section we review the initial approaches and some of the most promising and foundational studies undertaken in addressing the cellular delivery issue using the

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• reaction between 54 and 55 was performed in anhydrous methanol under an argon atmosphere to construct 56. The study on the in vitro drug release showed enhanced drug release at an acidic pH value in comparison to a neutral pH value. Importantly, the amount of DOX required for MCF-7 cells was decreased

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• intermediate or arenium ion 7 (Scheme 2). This occurs at the bridge as this offers greatest release of strain energy. Rearrangement to 8, as described by Cram and Hefelfinger, further lowers the strain energy of the cyclophane [36]. The carbocation could be trapped by a nitrate anion to give intermediate 9

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

• been in-vitro synthesized [32][42], being RNases resistant, and can release cargo in the cytoplasm of mammalian cells [32][33][43]. This work aims to evaluate the efficacy of CCMV VLP-VP28 dsRNA (VLP-dsRNAvp28) delivery against WSSV, by oral administration to shrimp through commercial feed pellets

• release. Although naked dsRNA can penetrate cell membranes when injected locally, it is rapidly degraded by plasma nucleases. The treated organisms with VLP-dsRNAvp28 by oral cavity obtained an 86% survival rate. However, during the oral cavity application treatment (VLP28-oral cav-3 and dsRNA28-oral cav

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• physicochemical nature of hydrophilic hydrogels. After the swelling experiment, samples were contacted to an aqueous RhB dye solution to investigate their dye releasing efficiency by gradually washing out the samples, in order to mimic a drug or nutrient release. One of the attractive applications of g-CN relies

• release which is highly beneficial for agricultural delivery systems. The grand outcome of embedded g-CN-based surface photomodification has significant advantages in terms of its non-toxic process and cost-efficient material resources. Pore substructuring In porous materials, the functionality of the

• separately in a capped glass vial containing 4 mL FTIC-albumin (2000 ppm) and FTIC-dextran (2000 ppm) solutions and left overnight. Afterwards, all samples were placed in another glass vial containing 4 mL distilled water to spectroscopically monitor the labeled molecule release process after 24 h. Cation

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

• previously described competitive colonisations of Ulva spp. [38][39]. Also, related species of Roseovarius sp. MS2 can often release unknown AGMPFs [29][40], which further foster the bacterial–algal interactions. As more species-specific metabolic markers become available, AP-SMALDI imaging will be a

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

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• based on the operating transition states [37][38]. A cyclic transition state is proposed in the reaction with sodium borohydride. In this transition state, the oxygen of the sulfinyl group interacts with the boron atom, facilitating the release of the hydride, directing the attack to the Si-face of the

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• amines with cyanoguanidine in refluxing water in the presence of CuCl2. The pink copper complexes were then treated with hydrogen sulfide to release the desired compounds. As a representative example, N1-butylbiguanide (buformin) was obtained as a hydrochloride salt, with a 47% yield (Scheme 2). Other

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• lipid, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and PEG-lipid, each with an essential role in the design (Figure 1). These lipids promote the effective distribution of the LNP in vivo as well as aid in effective cargo release from the endosome [1][37]. To this end, we herein

• this LNP formulation may not induce cytokine release syndrome in vivo [60][61]. Conclusion Taken together, we have shown that the LNP B9 formulation is safe, can traverse the BBB, and is readily taken up in multiple cell types. In the future, it will be interesting to explore whether increased uptake

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

• prochiral diol esters. The enzyme reacts enantiospecifically with the ester to release a chiral product, leaving the acyl group attached to the active site. In a second stage the achiral acyl group undergoes hydrolysis by water. In the desymmetrisation of diols (and diacids, below) kinetic amplification can

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• plausible mechanism shown in Scheme 14 explains the formation of azomethine ylide B by condensation of isatin with amino acid followed by release of a molecule of CO2 via A. The imine B undergoes 1,3-dipolar cycloaddition with the dipolarophiles 39. The cyclization yields the desired product 40 of the three

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• ; moreover, 53 and 54 can be mutually transformed. Excited state 53 reacts with diene 49, forming a double radical intermediate 55 that subsequently evolves to cyclobutyliminium ion 56, and then product 50 is provided after hydrolysis, along with the release of diamine 51. In 2020, Zhang and colleagues [25

• * under irradiation with light. Then, radical intermediate 113 is afforded via intermolecular electron transfer, followed by removing one molecule of carbon dioxide to give radical intermediate 114. Species 115 is formed through radical coupling in 114, providing the target product 111 with the release of

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

• release of DNA-hydrating ordered water molecules into the bulk solvent. Since the introduction of the N+ modification compensated for the negative charge on the DNA backbone, the change in the entropy costs for N+ON/DNA between 100 mM and 25 mM NaCl solutions was less than that for the unmodified duplex

[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

• ) and addition of diazo compounds at elevated temperatures with subsequent release of N2 (II). The cyclopropanation of C60 with stabilized α-halocarbanions, i.e., the Bingel reaction, is the most efficient way to synthesize methanofullerenes [76]. It is almost versatile; in the presence of a reactive

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

• usually synthetic polymers recalcitrant to decomposition, and hence liable to accumulate in landfills or the environment when discarded [5][6]. Not all plastics can be reused, and thus having limited economic value [7][8]. Plastics may release toxic compounds dangerous to human health and the habitat [9

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

• -(allylmethylsulfonio)propanoate (AllMSP), were synthesized and fed to marine bacteria from the Roseobacter clade. These bacteria are able to degrade DMSP into dimethyl sulfide and methanethiol. The DMSP analogues were also degraded, resulting in the release of allylated sulfur volatiles known from garlic. For unknown

• release sulfur volatiles [13][14] that are especially important headspace constituents from marine bacteria of the Roseobacter group [15][16][17]. In these organisms, sulfur volatiles are to a large extent generated from algal (DMSP), a metabolite that is produced in massive amounts by algae [18], thus

• not show the release of 27. Conclusion Bacteria from the Roseobacter group can degrade DMSP analogues with S-allyl groups including AllMSP and DAllSP, likely with the participation of the enzymes for DMSP (hydro)lysis and from the DMSP demethylation pathway. Because MeSH can also originate from other

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

• , and triflate 45f, which was isolated after basic workup of the reaction (59% yield) [63]. Hence, protonation of 44 led to dialkoxysulfonium triflate 47 along with the release of alcohol 9g. The subsequent formation of the excellent sultine leaving group 46 (assumed to be as good of a leaving group as

• 104–107 range [39][40][41][43][48][68]. Thus, while introducing one CF3 group dramatically alters the reactivity, an additional CF3 group does not seem to significantly impact the reactivity any further. The hypothesis of a ground-state strain release to explain this behavior was discarded as an

• proposed that upon heating, Ga(OTf)3 reacts with 63 to release an indolium ion 65 and forms an organogallium species 67 via intermediate 66, which, after protodemetallation, releases indole 62 and regenerates the catalyst. The retro-Friedel–Crafts reaction at 80 °C at the indole C3-position thus allows the

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

• from Aspergillus niger (AnFaeA, Figure 1C). Coloration is the result of successive reactions: (i) release of the free 5-bromo-4-chloro-indoxyl-3-ol by an enzyme cascade, wherein TxAbf-catalyzed cleavage of the glycosidic bond was made possible by the prior release by AnFaeA of the ferulate moiety [21

• of Faes was investigated (Figure 2), measuring 4NTC release by AnFaeA [42] at 40 °C. The enzyme-catalyzed reaction leads to the cleavage of the ester bond linking the ferulate to the linker–4NTC moiety, and thus to the accumulation of linker–4NTC. Therefore, working in a discontinuous mode, 4NTC is

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

• , Otting and co-workers have recently developed a synthetic strategy, based on a continuous exchange cell-free system (CECF), in which a key chitin-binding mutant of release factor RF1 can be removed under conditions that maintain the full activity of the S30 extract, thereby minimizing the incidence of

• 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

• cell lines [44]. Here, the incorporation of CF3 and CF3O groups as NMR reporters into the tumour-targeting drug conjugates enabled the direct investigation of the mechanism of the pro-drug metabolic cleavage and the pharmacophore release by real-time 19F NMR analysis. 19F NMR was also employed as a

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

• Ph3P+CF2−, which was used for the Wittig olefination of aldehydes and ketones. However, heating PDFA in nonpolar solvents (e.g., xylene at 90 °C) favors the dissociation of the ylide to release difluorocarbene which is able to effect the cyclopropanation of alkenes [34]. Trimethylsilyl

• . Further applications of free radical chemistry have developed through the use of radical initiators under comparatively mild conditions to form cyclopropylmethyl radicals, which can readily release their strain by opening to give homoallyl radicals. gem-Difluorocyclopropanes, because of their

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• immediate color change into dark red/brown took place after addition of complex 6b-Au(III), indicating a low stabilization of the coordinated diphenyl ligand and a fast release of Au. The de-coordination resulted in full conversion within 15 min in both reactions (Table 1, entries 3 and 6), compared to 24

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• small counterion release may contribute (likely, it is ionic repulsion due to the excess of positive charges (l < 1.0) in combination with changes in hydration shells that make this region endotherm). The last binding step starts at l = 0.16 (molar ratio 0.075), equal to 17 monomer units per poly

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• all synthetic works published in the last 25 years. Review Chemical ecology of Adalia bipunctata Individuals of Adalia bipunctata species (2-spot ladybird) display aposematic coloration reinforced by the production and release of remarkable amounts of reflex-fluid, in response to predator attack [29

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

• in the protein molecules due to proton uptake and release. Therefore, these events are strongly affected by the pH value and the ionic strength. Variation of the pH value or the ionic strength can result in substantial binding free energy changes [48] or changes in the binding preference [49