A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• after 24 h at 60 °C. Carvone isomerization was achieved at 60 °C for 24 h only combining the use of 10 mol % of capsule and 10 mol % of HBF4. Nevertheless, the reaction under identical conditions, but in the presence of 10 equiv of 3 as competitive guest, led only to a minimal inhibition of the reaction

• ), with quantitative yield after 20 h at 60 °C in the presence of 10 mol % of the capsule. The same reaction carried out with the capsule 16 and in the presence of 3 as competitive guest led to complete inhibition of the formation of the corresponding alkene (Figure 2D, Table 2, entry 2). This provides

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• -stoichiometric quantities of hosts because of the product inhibition effect, which arose from the entropic disadvantage of the need for binding two reactant molecules [39][40][41][42][43]. In this particular report, when the octahedral cage host A was used, the Diels–Alder reaction of 9-hydroxymethylanthracene

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• sialic acid derivatives in good yields and high purity via copper-catalysed azide–alkyne cycloaddition (CuAAC, click chemistry) and evaluated their activity towards TcTS and neuraminidase. Surprisingly, the compounds showed practically no TcTS inhibition, whereas ca. 70% inhibition was observed for

• neuraminidase in relation to the analogues bearing hydrophobic substituents and ca. 5% for more polar substituents. These results suggest that polarity changes are less tolerated by neuraminidase due to the big difference in impact of hydrophobicity upon inhibition, thus indicating a simple approach to

• differences in sialidases that need to be addressed in order to achieve selective inhibition. Keywords: inhibition; neuraminidase; sialic acid; trans-sialidase; 1,2,3-triazole; Introduction Amongst the diversity of glycans present in living organisms, N-acetylneuraminic acid (Neu5Ac, sialic acid) is

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• ], compounds 1−17 were evaluated for their inhibitory activities against LPS-induced nitric oxide (NO) production in RAW 264.7 mouse macrophages. All of them showed mild inhibitory activities with inhibition rates of 10–20% at a concentration of 50 μM (Table 2). Since coumarin derivatives were reported to have

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• reactions. The chain length in 14 should generally be suitable for effective HDAC inhibition and the thioester moiety might act as a prodrug as described for the natural HDAC inhibitor largazole. Further investigations are currently in progress. Naturally occurring HDAC inhibitors. Naturally occurring HDAC

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• Qiuxin Zhang Weiyi Tan Bing Xu Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA 10.3762/bjoc.18.17 Abstract Here we report the synthesis and effect on the cell viability of pyrrole-conjugated phosphopeptides. Encouraged by the selective inhibition of cancer

• from 1, are largely compatible with HeLa cells, while 1, at 400 μM, significantly inhibits HeLa cells. These results suggest that morphological transition or extensive self-assembly triggered by enzymatic reactions likely is necessary for the inhibition of HeLa cells by EISA. This work, thus, provides

• investigated the physical properties (enzyme-catalyzed hydrogelation or supramolecular structural transformation) [62][70] and biological properties (cell viability, biostability, and cell-selective growth inhibition) [43][62] of the naphthylacetyl N-terminal-capped phosphopeptides. These studies have produced

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• ][14], ddI (didanosine) [15], d4T (stavudine) [16][17], 3TC (lamivudine) [18][19] and AZT analogues were synthesized and evaluated towards inhibition of HIV reverse transcriptase (HIV RT). However, the toxic side effects associated with these molecules and development of drug-resistant viruses

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• evaluated against their antioxidant activity and exhibited promising activity. Protein tyrosine phosphatase 1B (PTP1B) is essential in the dephosphorylation of the activated insulin receptor, and inhibition of this enzyme would be an excellent strategy for the treatment of type 2 diabetes. Ahn and co

• -workers [82] synthesized and evaluated several 1,2-naphthoquinones substituted at position C4 with alkyl- or arylamino groups for their inhibition of the PTP1B protein. Furthermore, to discover new effective anti-inflammatory and analgesic agents, Gouda and co-workers [83] synthesized various compounds in

• intracellular ROS and includes inhibition of tubulin polymerization (Scheme 9). Semicarbazides and thiosemicarbazides are substances used to identify aldehydes and ketones, are very versatile in the synthesis of heterocycles, and have several applications in the preparation of important drugs. Nucleophilic

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• P5.2 of stapled peptide P5 shows an almost five times higher binding affinity (Kd = 258 ± 43 nM) compared to the linear reference peptide P6 (Kd = 1241 ± 162 nM, Figure 2) in the competitive FP assay. Isomer P5.1 was only isolated in insufficient amounts. Hence, a satisfactorily converging inhibition

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• inhibition upon exposure to 4-anilinoquinazolines and compounds with the same scaffolds (erlotinib, gefitinib, and verubulin), and to positive control doxorubicin (MTT assay after treatment for 72 h). Supporting Information Supporting Information File 282: Experimental procedures, characterization data

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• cellular targets known for antituberculosis drugs and all the different chemical structures (inhibition of cell wall synthesis, disruption of the plasma membrane, DNA-gyrase, etc.) the next work focused on determining the exact biological mechanism and docking studies could not be executed. Conclusion The

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• tubular cells HK2. (−)-Codonopsinol B (1) and its N-nor-methyl analogue 2; known inhibition activities against α-glucosidases from: (a) Bacillus stearothermophilus lyoph., (b) yeast [2]. Molecular structure of N-Cbz-protected pyrrolidine 12 confirmed by single-crystal X-ray crystallographic analysis

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• ) showed a weak TPC2 inhibition at 100 µM. The nine other alkaloids did not significantly inhibit human TPC2, whereas tetrandrine and cepharanthine concentration-dependently blocked with IC50 values of 31/21 µM and 3.6/57 µM (Figure S2A and Figure S2B in Supporting Information File 1). Note that TPC2

• population indicates inhibition of P-glycoprotein. However, none of the tested compounds was able to retain calcein, indicating no P-glycoprotein inhibition. Tetrandrine served as positive control (Figure 5C). In line with that, none of the compounds restored sensitivity of VCR-R CEM cells to the P

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• incorporated into the growing DNA strand. However, the absence of a 3'-hydroxy group prevents further strand elongation. The anticancer and antiviral activity of 2’,3’-dideoxynucleosides is mainly based on inhibition of DNA synthesis, either through the chain termination process or by competitive inhibition [3

• natural nucleosides with β-ᴅ-configuration in the carbohydrate part. These molecules are known to have a common HIV transcriptase inhibition mechanism, in which cytoplasmic enzymes progressively phosphorylate the analogues to 5'-triphosphates. This then competes with the naturally occurring nucleoside

• nucleic acid components. Therefore, it was assumed until recently that effective inhibition of the metabolic enzyme is only possible by ᴅ-nucleoside analogues, which have the stereochemistry of natural nucleosides. This was proved to be untrue when the antiviral activity of 1,3-oxathiolane nucleosides

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• used to treat joint pain and postoperative pain [6] (Figure 1). Ellipticine was considered to be based mainly on DNA intercalation and topoisomerase II inhibition [7]. Midostaurin and carvediol have been approved by the FDA for tumor therapy and treatment of congestive heart failure [8]. On the other

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• human cancer cell lines and inhibition of the chemokine receptor CCR5, make them attractive synthetic targets. This review article highlights the recent synthetic methodologies and briefly summarizes their biological activities. Keywords: brevipolides; 5,6-dihydro-α-pyrone; Furukawa-modified Simmons

• all the centers of the stereochemical brevipolides but in the mirror image of the natural configuration. After sequential ring-closing metathesis, base-promoted olefin migration, and MEM removal, the ent-brevipolide H (ent-8) was obtained. This compound showed inhibition activity in the preliminary

• ]. These seven compounds, 1–7, were also evaluated for enzyme-based ELISA NF-κB and proteasome inhibition assays (Table 2, entries 1–7), but only brevipolide G (7) and brevipolide C (3) showed significant activities with ED50 values of 15.3 and 38.0 μM, respectively (Table 2, entries 7 and 3) [4]. Lastly

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• metronidazole derivatives. The antimicrobial (antifungal and antibacterial) activity of the prepared compounds was studied. All compounds (except 2 and 3) showed a potent inhibition rate of fungal growth as compared to control and metronidazole. The synthetic compounds also showed higher bacterial growth

• , fungal growth under compound 5e and compound 7c treatment was detected 2.8, 2.7 folds and 2.5, 2.6 folds less, respectively. All of the synthesized compounds except compounds 2 and 3 showed a higher inhibition rate of fungal growth as compared to the control and metronidazole (Figure 7 and Table 3). The

• inhibition zones were recorded after 7 days of treatment and compared with growth area of fungi growing in control conditions. Antibacterial activity To determine the bacterial growth inhibiting effects of compounds, bacterial OD600 was measured at different time points i.e., 12, 24, 36 and 48 h (Figure 8

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• stereochemistry, but they showed quite different inhibition effects on NO production (IC50 55.0 μM, 2; IC50 > 500 μM, 5). The MTT cell viability test suggested that all the compounds had no cytotoxic effect on BV-2 cell survival at a concentration of 20 μM. Compounds 1–19 were also tested for their

• 17–19. The structural characterization of the new compounds was conducted based on the analysis of their spectroscopic and spectrometric data, and chemical methods. All isolated compounds were tested for their antineuroinflammatory and neuroprotective activities. Compound 14 showed inhibition effects

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

• observed, particularly into the soft tissue sarcoma spheroids, indicating that the TPP conjugation improved the internalization into tumours for MPM-NP2-TPP, despite being slightly less stable than the non-conjugate micelles. The TPP-particles were further investigated for spheroid growth inhibition using

• TPP to zwitterionic particles accelerated its anticancer performance in terms of spheroid uptake and tumour growth inhibition, while no anticancer enhancement was detected when the PEGylated micelle was conjugated with a mitochondrial agent. In conclusion, the conjugation of TPP to MPM-NP2 gave the

(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

• , with IC50 values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1

• reference [26]. In this context, the intent is to replace the amide group present in IMT by the 1,2,3-triazole nucleus, similar to compound 3 described in the literature by Li and co-workers, which showed a good inhibition profile of the myelogenous leukemia K562 cell line [27]. Considering the good

• inhibition profile of substance 3 against K562 cells, we proposed, through the molecular simplification strategy, the derivatives 1a and 1b, which have hydroxyalkyl groups replacing the phenylpiperazine group. The hydroxymethyl and hydroxypropyl groups were chosen because they were not evaluated in the

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

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

• 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

• ability of the products. Up to >80% inhibition of the amyloid-β peptide aggregates were achieved with these compounds, with the highest activity found for the 4-N-methylpiperidyl derivative. Ethers The synthesis of the bis(indol-6-yl) ether 175 was performed by Chai in 2017. Their protocol used a Cu(OAc)2

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• turned on. This can be explained by a low oxygen inhibition, which is an advantage for different applications where the photopolymerization under air is required. As shown in Figure 2 and Figure 3, only CNa, CBPh3, CI3, and CI10 show a long inhibition time, and this can be ascribed to the low absorption

• governing the formation of initiating radicals. The slightly lower reactivity of NPG vs DABA can probably be ascribed to a lower production of initiating radicals in this case, rendering the associated PIS slightly less efficient to overcome the oxygen inhibition. This behavior has already been observed in

• photopolymerization [7]. Remarkably, in this work, no inhibition time was observed while using different dyes, i.e., CBPh1, CBPh4; CI1, and CI5, as compared to IR 813. All these observations suggest that the proposed photoinitiating NIR dye/iod/amine compositions result in high-performance NIR-photosensitive systems

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• needed to accomplish procedures that allow recycling and lower catalyst loading, intertwined with the use of green solvents, in order to provide efficient and sustainable synthesis of these important pharmacologically active compounds. Coumarin-derived commercially available drugs. Inhibition of

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