Convenient modification of the Leimgruber-Batcho indole synthesis: reduction of 2-nitro-β-pyrrolidinostyrenes by the FeCl3–activated carbon–N2H4∙H2O system

Taydakov, Ilya V.; Dutova, T. Ya.; Сидоренко, Е. Н.; Krasnoselsky, S. S.

doi:10.1007/s10593-011-0776-2

Cited by 11 publications

(3 citation statements)

References 10 publications

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“…The calculated MW for C11H13NONa was 198.0895, whereas the actual MW was 198.0898. The 1H and 13C NMR spectral data of compound P4-2 were consistent with previously published literature ( Taydakov et al, 2011 ).…”

Section: Methodssupporting

confidence: 89%

Targeting the N-Terminus Domain of the Coronavirus Nucleocapsid Protein Induces Abnormal Oligomerization via Allosteric Modulation

Hsu

Chen

Lin

et al. 2022

Front. Mol. Biosci.

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Epidemics caused by coronaviruses (CoVs), namely the severe acute respiratory syndrome (SARS) (2003), Middle East respiratory syndrome (MERS) (2012), and coronavirus disease 2019 (COVID-19) (2019), have triggered a global public health emergency. Drug development against CoVs is inherently arduous. The nucleocapsid (N) protein forms an oligomer and facilitates binding with the viral RNA genome, which is critical in the life cycle of the virus. In the current study, we found a potential allosteric site (Site 1) using PARS, an online allosteric site predictor, in the CoV N-N-terminal RNA-binding domain (NTD) to modulate the N protein conformation. We identified 5-hydroxyindole as the lead via molecular docking to target Site 1. We designed and synthesized four 5-hydroxyindole derivatives, named P4-1 to P4-4, based on the pose of 5-hydroxyindole in the docking model complex. Small-angle X-ray scattering (SAXS) data indicate that two 5-hydroxyindole compounds with higher hydrophobic R-groups mediate the binding between N-NTD and N-C-terminal dimerization domain (CTD) and elicit high-order oligomerization of the whole N protein. Furthermore, the crystal structures suggested that these two compounds act on this novel cavity and create a flat surface with higher hydrophobicity, which may mediate the interaction between N-NTD and N-CTD. Taken together, we discovered an allosteric binding pocket targeting small molecules that induces abnormal aggregation of the CoV N protein. These novel concepts will facilitate protein-protein interaction (PPI)-based drug design against various CoVs.

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Section: Methodssupporting

confidence: 89%

Targeting the N-Terminus Domain of the Coronavirus Nucleocapsid Protein Induces Abnormal Oligomerization via Allosteric Modulation

Hsu

Chen

Lin

et al. 2022

Front. Mol. Biosci.

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“…Since the structures of all three target bCSE inhibitors, i.e., NL1, NL2, and NL3, are based on a fragment of 6-bromoindole or its derivative, the initial step was to choose a convenient synthesis of 6-bromoindole 4 as one of the main building blocks in amounts of at least several tens of grams. About a dozen of methods for its synthesis can be found in the literature [4][5][6]; a complete description of their drawbacks and advantages (along with a synthesis of another important natural derivative, 6-bromotryptamine) was summarized in the recent review article [7]. However, many reported methods possess problems with scalability, the availability of initial reagents, and low yields.…”

Section: Synthesis Of 6-bromoindolementioning

confidence: 99%

“…Thus, with 17 as the key reagent, the main part of the NL3 synthetic sequence consists of four steps (Figure 6). 6-Bromoindole 4 is first alkylated with propargyl bromide in the presence of sodium hydride to produce propargylindole 18 [20], which is then introduced into the [3+2]-cycloaddition reaction with ethyl diazoacetate at the triple bond to form the pyrazole ring in product 19 [4]. Thus, with 17 as the key reagent, the main part of the NL3 synthetic sequence consists of four steps (Figure 6).…”

Section: Synthesis Of Nl3 Inhibitormentioning

confidence: 99%

Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3

et al. 2023

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Bacterial cystathionine γ-lyase (bCSE) is the main producer of H2S in pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of gram quantities of two selective indole-based bCSE inhibitors, namely (2-(6-bromo-1H-indol-1-yl)acetyl)glycine (NL1), 5-((6-bromo-1H-indol-1-yl)methyl)- 2-methylfuran-3-carboxylic acid (NL2), as well as a synthetic method for preparation 3-((6-(7-chlorobenzo[b]thiophen-2-yl)-1H-indol-1-yl)methyl)- 1H-pyrazole-5-carboxylic acid (NL3), have been developed. The syntheses are based on the use of 6-bromoindole as the main building block for all three inhibitors (NL1, NL2, and NL3), and the designed residues are assembled at the nitrogen atom of the 6-bromoindole core or by the substitution of the bromine atom in the case of NL3 using Pd-catalyzed cross-coupling. The developed and refined synthetic methods would be significant for the further biological screening of NL-series bCSE inhibitors and their derivatives.

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Reductive Cyclization of 2‐Nitro‐ and β‐Nitrostyrenes, 2‐Nitrobiphenyls, and 1‐Nitro‐1,3‐Dienes to Indoles, Carbazoles, and Pyrroles

Söderberg

Berkowitz

2022

Organic Reactions

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This chapter presents a comprehensive review of reductive cyclizations of 2‐nitro‐ and β‐nitrostyrenes, 2‐nitrobiphenyls, and 1‐nitro‐1,3‐dienes to furnish indoles, carbazoles, and pyrroles, respectively, as well as heteroatom analogs thereof. Two variations of the reductive cyclization are discussed: the Cadogan–Sundberg reaction, which is mediated by ternary phosphorus compounds, and the Watanabe–Cenini–Söderberg reaction, which employs a palladium catalyst in the presence of carbon monoxide. A few closely related reductive cyclizations are also presented, as are comparisons with other cyclizations that form the nitrogen–carbon bond of indoles and derivatives.

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Convenient modification of the Leimgruber-Batcho indole synthesis: reduction of 2-nitro-β-pyrrolidinostyrenes by the FeCl3–activated carbon–N2H4∙H2O system

Cited by 11 publications

References 10 publications

Targeting the N-Terminus Domain of the Coronavirus Nucleocapsid Protein Induces Abnormal Oligomerization via Allosteric Modulation

Targeting the N-Terminus Domain of the Coronavirus Nucleocapsid Protein Induces Abnormal Oligomerization via Allosteric Modulation

Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3

Reductive Cyclization of 2‐Nitro‐ and β‐Nitrostyrenes, 2‐Nitrobiphenyls, and 1‐Nitro‐1,3‐Dienes to Indoles, Carbazoles, and Pyrroles

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