Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• evaluate the changes in cellular uptake or the toxicity of the conjugated arsenic drug. Attachment of TPP onto the PISA particles however was found not to enhance the mitochondrial accumulation, but it did influence overall the biological activity of pMPC-based particles in 2D and 3D cultured sarcoma SW982

• have shown great promise as these drugs inhibit the function of mitochondria while showing overall reduced systemic toxicity. PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsenonous acid) [2][3], a trivalent arsenical drug, was developed by Hogg and co-workers and is currently in clinical trials [4

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• for designing new series of substances with greater potency and less toxicity than IMT, with lesser effects for the patient. Molecular docking Validation of the molecular docking protocol was performed through redocking of the IMT complexed to the BCR-Abl-1 structure (PDB code: 3PYY) [37]. Thus, the

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• of synthetic routes for modern pharmaceuticals [21][22]. Over the past two decades, nickel has emerged as an attractive alternative to palladium due to its relative earth-abundance, less toxicity, and inexpensiveness. Despite the fact that the nickel-catalyzed cross-coupling reactions represent a

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

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

• few of them become approved, due to their toxicity or other issues related to their applicability. Therefore, synthetic methodologies that facilitate the successful production of potential biologically active molecules have a relevant role in the organic synthesis research field. One of the key

• involving organochromium species generated from alkyl halides [115][116]. Whereas its toxicity has hindered the use of Cr(VI) in organic synthesis, the less toxic Cr(III) and Cr(II) salts have been exploited as plausible catalysts in organic synthesis [117][118]. A good example is a redox-neutral reaction

• toxicity of some chromium species, based on the above cited examples, by using this metal valuable biologically active molecules can be safely obtained. The correct, judicious, and optimized application of chromium-based catalysts can lead to the easier access of several drugs. Further studies in this area

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• endogenous nucleic acid targets, thereby inhibiting the gene expression. Although ASOs have great potential in the treatment of many diseases, the search for favorable toxicity profiles and distribution has been challenging and consequently impeded the widespread use of ASOs as conventional medicine. One

• derivative group, when conjugated to the C-5 position on 2’-deoxyuridine (Table 1B, 12), improved antisense activity while reducing toxicity [39]. In addition, a 15-mer PS-ASO, modified with the C-5 tris-aminated 2’-deoxyuridine 12, improved anti-HIV activity and reduced cytotoxicity relative to the

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• therapeutic potential of ergot alkaloids as early as 1582 and used it for abortion or to aid childbirth. The ecological significance of ergot alkaloids remains unclear, but they are assumed to be a feeding deterrent due to their toxicity and bad taste [25][26][27][28]. To trigger the synthesis of new SMs a

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• on the pyridinium nuclei, and were the first reactive, easy-to-handle fluorinating agents with wide application [28][29]. The work continued with additional disclosures until 1991 [30][31][32][33][34]. Before that, reactive fluorinating reagents were difficult to handle because of toxicity, a

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

• organic synthesis. Among the 3d metals, manganese catalysts have gained increasing attention for late-stage diversification due to the sustainability, cost-effectiveness, ease of operation, and reduced toxicity. Herein, we summarize recent manganese-catalyzed late-stage C–H functionalization reactions of

• natural abundance, cost-effectiveness, and low toxicity. In addition, it presents variable oxidation states (−3 to +7), which enable diverse catalytically active manganese complexes, providing characteristic reaction profiles. Since the first pioneering manganese-mediated reaction for accessing

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

• notably lagged behind and is still limited by insufficient bioavailability and difficulties with tissue specific delivery. Relatively high doses are required to overcome poor cellular uptake and endosomal entrapment, which increases the risk of toxicity. These limitations remain unsolved problems waiting

• ]. However, the uptake of most PNA–CPP conjugates is limited by endosomal entrapment. While the uptake can be improved either by increasing the concentration of PNA–CPP conjugates or by using endosomolytic compounds (for example, chloroquine or calcium ions) this leads to toxicity that is not viable for in

• administered PNA–penetratin conjugate (3 × 10 μL of 150 μM) caused a 40% decrease in 125I-galanin binding in spinal cord sections compared to rats treated with the saline control. The PNA–peptide conjugates showed no toxicity in these studies [171]. Boffa and co-workers conjugated antigene PNA to a nuclear

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

• capsids or virus-like particles (VLPs) [30][31][32] lacking the viral genome. Their small size (20–140 nm), allows them to permeate the cell membranes without causing toxicity or immune response in the treated organisms [30][32][33][34][35][36]. In particular, the VLPs derived from plant viruses are

• [60]. The CCMV has been reported to be biocompatible in mammals, testing the wild-type virus in mice [32][61]. However, there were no studies to demonstrated non-toxicity in other species such as crustaceans and fish. Therefore, before performing the bioassays with VLP-dsRNAvp28, this study evaluated

• the toxicity of wt CCMV in healthy shrimp. The bioassay was carried out for three weeks, and the shrimp showed no symptoms of any disease or apparent abnormality when treated by IM (up to 20 µg of CCMV per shrimp). Higher doses of dsRNAvp28 (200 µg) per WSSV infected shrimp by IM injection were also

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

• been also an advanced intermediate in the synthesis of alkaloids. For instance, hydrogenation of 117 yielded (+)-coniine (118), the major alkaloid extracted from poison hemlock and responsible for its toxicity, as its hydrochloride, and N-Boc protected derivative of 117 submitted to Wacker oxidation

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

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

• compared to second generation 2'-O-MOE antisense oligonucleotides [162][163]. The cEt also demonstrate an improved toxicity profile in comparison to standard LNA ASOs [162]. The arduous synthesis of the nucleoside analogues has been refined to minimize the number of needed stereochemical adjustments and

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

• ]. Clinical trial safety assessments of this formulation showed no liver toxicity and no immune stimulation, with ≈10% of trial participants experiencing mild to moderate adverse events upon administration [38]. It includes encapsulation of siRNA by a mixture of lipid components, such as an ionizable cationic

• aptamers and peptides within the LNPs or to optimize the ratio of LNPs to cells in order to reduce toxicity in any cell line tested. Discussion LNPs represent an increasingly popular modality for cargo delivery. The vast improvements in lipid design and architecture have resulted in several successful LNP

• -driven vaccines and therapeutics, including two RNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines [46], as well as an siRNA–LNP for the treatment of a transthyretin amyloidosis [36]. However, further improvements in toxicity profiles, cargo delivery, and cell or organ

[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

• to dementia have been demonstrated [39][40]. Moreover, it is noted that the almost nonexistent toxicity of the C60 derivatives allows to use them in living systems without negative consequences. Studies on the use of C60 derivatives in micro- and nanoelectronics are also important and very promising

• first gave ester 181 and then acid 182 (Scheme 31), the sodium and potassium salts of which are well soluble in water. The compound has antiviral and anticancer activity as well as pronounced antioxidant properties combined with low toxicity. Diarylmethanofullerene 183 was synthesized according to

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

• kinetics, cost of metals, toxicity, difficulty in catalyst reusing and need of downstream processing. Significant efforts have thus been made to develop greener and sustainable catalytic systems featuring high efficiency under mild conditions. The use of sodium carbonate or bicarbonate as ecofriendly

• catalysts in the form of ionic liquids (ILs) [209]. Advantages of metallated ILs include low flammability, high thermal stability and versatility. However, their “greenness” and toxicity are still debated [225][226]. Thus, amim[ZnCl3] (amin = 1-allyl-3-methylimidazolium, Table 4, entry 1) [227] and amim

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

• to its toxicity, the oxidation rate affording trans-diols was very slow in comparison to that for cis-diols. Using an even longer reaction time and stoichiometric amount of the reagent, diol 5 was not oxidized to the corresponding dicarbonyl compound 8. However, using NaOCl·5H2O as an oxidant [31

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

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• , respectively) gave the two highest results, but the use of dioxane is best avoided due to its toxicity. Except for hexane (only 6% ee, Table 1, entry 13), which resulted in an almost racemic product presumably due to solubility issues, all other solvents afforded the target SMA adduct with similar moderate ee

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

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• agreement with the NMR data measured by us, what leaves no reasonable doubt that the synthesized structure 1 is identical with the natural product. Decarboxyaltenusin (1) was screened for toxicity towards human HeLa cells but proved nontoxic at biologically relevant concentrations and showed an LD50 value

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• times if compared with toluene. We therefore selected CPME as the most suitable solvent for our purposes. Interestingly, besides being characterized by low toxicity, CPME has a very low affinity to water, making it suitable for moisture sensitive reactions, without previous distillation [31][32][33

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

• as an early warning signal to the attacker. The fluid toxicity and bitterness, added to the characteristic odor of these insects, have been regarded as a protection against insect or vertebrate predators [3]. Bicyclic ring systems bearing a nitrogen bridge are often found in nature [4][5][6]. Typical

• concentration of coccineline found in C. septempunctata [31]. This difference may occur to compensate (−)-adaline's lower toxicity than coccineline. Biosynthetic studies carried out by Laurent et al. [33][34] showed that adults of A. bipunctata incubated in vitro with [14,14,14-3H3]myristic acid incorporated

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• (betulinic acid) and 8 (apigenin) also exhibited significant activity with IC50 values of 4.3 and 16.6 μM, respectively. Tolstikov et al. reported that betulin (9) and its derivatives showed antiviral and antitumor effects [41]. Interestingly, betulinal (11) has an advantage in view of toxicity as compared

• compounds, only compound 8 (apigenin) exhibited a weak activity on the NGF release with a stimulation level of 127.8 ± 2.0% without displaying cell toxicity (100.9 ± 0.6%). Conclusion A new megastigmane-type norsesquiterpenoid glycoside 1 was isolated along with 11 known compounds from the MeOH extract of C