Carbazole Framework Research Articles

Photophysical Properties of Emissive Pyrido[3,2-c]carbazole Derivatives and Apoptosis Induction: Development towards Theranostic Agents in Response to Light Stimulus.

Pyridocarbazole moieties are present in many natural products, such as olivacine and ellipticine, and their derivatives are well-known anticancer agents. To develop functional therapeutic and diagnostic compounds, three emissive pyrido[3,2-c]carbazole derivatives, PC-X, containing secondary or tertiary amine groups, were synthesized from an aminoquinoline derivative using a palladium complex as the catalyst. X-ray diffraction analyses revealed that PC-X showed highly planar structures between the pyridine ring and the carbazole framework, exhibiting high fluorescence intensities along with solvatochromic behavior. Imaging of HeLa cells treated with PC-X showed no specific accumulation into the organelles; however, a comparative examination showed that the accumulation in mitochondria was the highest as compared to nuclei and lysosomes. Cytotoxicity analysis using HeLa cells showed that PC-H, containing a secondary amine group showed the highest cytotoxicity (IC50 ≈20 μm) as compared to another PC-X having a tertiary amine group. Colocalization with MitoTracker, a typical mitochondrial staining dye, showed apoptosis-like behavior with remarkable appearance of blebbing during irradiation with near UV light (403 nm), suggesting that the PC-H may not only behave as a fluorescence probe for the imaging organelles, but also as a therapeutic agent for inducing apoptosis in HeLa cells, thereby functioning as a theranostic agent.

Design of a ratiometric two-photon fluorescent probe for dual-response of mitochondrial SO2 derivatives and viscosity in cells and in vivo

The content of sulfur dioxide (SO2) in mitochondria is related to various physiological and pathological processes. The irregular viscosity in mitochondria would result in mitochondria disorders. In this research, a novel ratiometric two-photon fluorescent probe (MBCB) based on carbazole framework has been strategically designed and synthesized for dual-detection of mitochondrial SO2 derivatives and viscosity. The results show that probe MBCB is capable of responding to SO2 derivatives and viscosity using dual-color imaging. MBCB can not only recognize SO2 derivatives utilizing a ratiometric change of fluorescent intensity (I434 nm/I600 nm), but also shows a high sensitivity and selectivity for monitoring SO2. On the other hand, the fluorescent intensity ratio (I567 nm/I415 nm) of MBCB increased with the increment of viscosity and exhibited a good logarithmic linear relationship between the ratio and viscosity (R2 = 0.99). Satisfactorily, probe MBCB has a good targeting ability to mitochondria and a low cell cytotoxicity, and can be successfully applied to detect HSO3− in living cells and in vivo. Furthermore, the probe can visualize the change of mitochondrial viscosity induced by nystatin.

A General Carbazole Synthesis via Stitching of Indole-Ynones with Nitromethanes: Application to Total Synthesis of Carbazomycin A, Calothrixin B, and Staurosporinone.

A new, one-pot domino benzannulation reaction between indole-3-ynones and various nitromethane derivatives has been explored for a general entry to diversely functionalized carbazole frameworks (28 examples). The scope of this new benzannulation has been extended to variants like 2-chloroindole-3-ynones to eventuate in chemo-differentiated 1,2,3,4-tetrasubstituted carbazoles with retention of the nitro group. The efficacy of this strategy has been demonstrated through concise total synthesis of natural products, viz. carbazomycin A, calothrixin B, and staurosporinone (K252c).

An Efficient Selectfluor-Mediated Oxidative Thio- and Selenocyanation of Diversely Substituted Indoles and Carbazoles

A facile Selectfluor-mediated oxidative method for direct introduction of SCN and SeCN groups into diversely substituted indoles and carbazoles is described, by employing readily available thiocyanate and selenocyanate salts, and the scope of the method is underscored by providing 24 examples. The feasibility to sequentially introduce SCN followed by SeCN on a carbazole framework and to synthesize the corresponding S-tetrazole and Se-tetrazole derivatives is also demonstrated.

Ultrafine silver nanoparticles supported on a covalent carbazole framework as high-efficiency nanocatalysts for nitrophenol reduction

A novel covalent micro/macro-porous polymer (CMP), CZ–TEB, is synthesized and then Ag NPs are immobilized on it, and the normalized rate constant (knor) of the Ag0@CZ–TEB catalyzed reduction reaction of 4-NP to 4-AP reaches up to 21.49 mmol−1 s−1.

Synthesis and structure–property correlation of blue fluorescence isomer emitters based on rigid pyrazine-bridged carbazole frameworks

The unsymmetrical linking model ofTCz-3,9PA-TCzbased on pyrazine and carbazole moieties is feasible to produce efficient and stable blue-light emitters.

Enantioselective Total Synthesis and Assignment of the Absolute Configuration of the Furo[3,2- a]carbazole Alkaloid Furoclausine-B.

We describe the first enantioselective total synthesis and the assignment of the absolute configuration of the furo[3,2- a]carbazole alkaloid furoclausine-B. As key steps for our approach we used a palladium(II)-catalyzed double C-H-bond activation for the construction of the carbazole framework, a Shi epoxidation, and an intramolecular opening of the epoxide for annulation of the dihydrofuran moiety.

Cu(I)-/Base-Mediated Domino [5 + 3 + 1] Annulation for Highly π-Extended Carbazole Frameworks and DFT Mechanistic Insights.

An efficient synthesis of highly π-extended carbazoles is described via an unexpected domino [5 + 3 + 1] annulation approach. The Cu(I)-/base-promoted reactions of 2-nitrocinnamaldehydes with benzyl cyanides provide diverse benzo[ b]carbazoles. The reaction is proposed to proceed via a sequential Michael addition/intramolecular addition of an enol into a nitro group, 6π- electrocyclization, and the final oxidative aromatization as supported by density functional theory calculations. Some of the synthesized carbazoles showed significant potential in fluorescence sensing of Cu2+ ions.

Synthesis of Novel 3‐N‐substituted Carbazole Derivatives and Evaluation of their Abilities to Inhibit Platelet Aggregation

The carbazole moiety exhibits various biological activities, including anticancer, antiviral, anti‐inflammatory, and antimicrobial activities; some compounds containing the moiety also inhibit platelet aggregation. In the present study, we synthesized a series of 3‐N‐substituted carbazole derivatives and evaluated their abilities to inhibit in vitro platelet aggregation induced by collagen (5 μg/mL). Of the synthesized compounds, compound 5q (JSCa15), with a urea linkage within the carbazole framework, exhibited the strongest inhibitory activity (98.25% at 30 μM). Interestingly, reduction of the nitro group of compound 5q to an amine exhibited significantly decreased activity (compound 5r, 5.18% at 30 μM). Also, substitution of the urea moiety of compound 5q with a carbamate moiety resulted in a considerable loss of activity (compound 8a, 5.91% at 30 μM). These results suggest that the urea moieties and nitro groups of 3‐N‐substituted carbazole derivatives may play key roles in inhibiting in vitro platelet aggregation induced by collagen.

First Total Synthesis of 7-Isovaleryloxy-8-methoxygirinimbine

We describe the first total synthesis of the pyrano[3,2-a]carbazole alkaloid 7-isovaleryloxy-8-methoxygirinimbine, using a palladium(II)-catalyzed double C–H-bond activation for construction of the carbazole framework and a phenylboronic acid catalyzed annulation of the pyran ring as key steps.

Tipping the Balance between Ligand and Metal Protonation due to Relativistic Effects: Unusually High Proton Affinity in Gold(I) Pincer Complexes.

Quantum theoretical studies show that the extremely high proton affinity at the metal center of the unusual T-shaped (LXL)AuI -pincer complex, consisting of a carbazole framework and two mesoionic carbenes, is caused by relativistic effects. This brings the basicity of the AuI center in line with the electron-rich nitrogen atom of the carbazole ring system, resulting in one of the highest proton affinities for a neutral molecule.

A novel synthesis of octahydropyrido[3,2-c]carbazole framework of aspidospermidine alkaloids and a combined computational, FT-IR, NMR, NBO, NLO, FMO, MEP study of the cis-4a-Ethyl-1-(2hydroxyethyl)-2,3,4,4a,5,6,7,11c-octahydro-1H-pyrido[3,2-c]carbazole

In this study, we performed a novel synthesis of the octahydropyrido[3,2-c]carbazole derivative 6 from 1 in five steps with a 34% overall yield. We also developed a unique compound 2 by a cyclization reaction from the cyanoethylation of compound 1, which is an intermediate step in the synthesis of Aspidospermidine. The parent compound of Aspidospermidine alkaloids, comprise a large family of diverse structures. As a result, we obtained octahydropyrido[3,2-c]carbazole (6)and the proposed method may be applicable to other alkaloids. All quantum chemical calculations of the cis-4a-Ethyl-1-(2-hydroxyethyl)-2,3,4,4a,5,6,7,11c-octahydro-1H-pyrido[3,2-c]carbazole have been performed with the DFT/B3LYP and HF methods by using the Gaussian 09W software package. The most stable conformer obtained from the Potential Energy Surface (PES) scan analysis at the B3LYP/6-31G** level of theory in the gas phase was used as the starting structure of the title compound to further computational analysis. The Natural Bond Orbital (NBO) and NLO analyses were performed to evaluate the intra-molecular interactions contributing to the molecular stability and to predict the optical properties of the title compound, respectively. Gauge-Independent Atomic Orbital (GIAO) approach was used to determine the 1H and 1C NMR chemical shifts of the title compound by subtracting the shielding constants of TMS at both methods. The calculated vibrational frequencies of the title compound were assigned by using the VEDA program and were scaled down by using the scaling factor 0.9668 for B3LYP/6-311++G(d, p) and 0.9050 for HF/6-311++G(d, p) to improve the calculated vibrational frequencies. The FMO (frontier molecular orbital) analysis was evaluated to predict the chemical and physical properties of the title compound and the HOMO, LUMO, and MEP diagrams were visualized by GaussView 4.1 program to present the reactive site of the title compound.

First Total Synthesis of the Cytotoxic Carbazole Alkaloid Excavatine‐A and Regioselective Annulation to Pyrano[2,3‐a]carbazoles and [1,4]Oxazepino[2,3,4‐jk]carbazoles

We describe the first total synthesis of the cytotoxic carbazole alkaloid excavatine‐A. The carbazole framework was constructed through double C–H bond activation of a diarylamine by using our palladium(II)‐catalyzed oxidative cyclization. Treatment of the intermediate 8‐hydroxycarbazoles with prenal and different additives led either to pyrano[2,3‐a]carbazoles or to [1,4]oxazepino[2,3,4‐jk]carbazoles. The pyran annulation was investigated to determine the influence of substitution pattern, additives, and reaction time on the selectivity.

Highly Site‐Selective and Direct Ortho‐C−H Nitration, Trifluoromethylation and Cyanation at the C1‐Position of Carbazole Frameworks

AbstractWe report a concise, versatile, and practical method for ortho‐C−H mononitration, monotrifluoromethylation and monocyanation of carbazole cores via a transition‐metal‐catalyzed reaction using an appropriate functional group source. The significant advantage of this transformation is the generation of highly site‐selective direct C1–heteroatom bonds that are geometrically difficult to access, in good to excellent yields.

Nucleophilic T-Shaped (LXL)Au(I)-Pincer Complexes: Protonation and Alkylation.

We report the synthesis and reactivity of unusual T-shaped (LXL)Au(I)-pincer complexes, based on a carbazole framework flanked by two mesoionic carbenes (MICs). In contrast to other Au(I) complexes, these complexes react with electrophiles. Protonation and alkylation occur either at the metal or the ligand, depending on steric factors. Of particular interest, protonation at gold leads to an unprecedented cationic Au(III) hydride, which gives a 1H NMR resonance at δ -8.34 ppm. The reactivity of this "hydride", however, shows protic and not hydridic behavior.

In vitro alternatives: Evaluation and recommendations for the reconstructed 3D skin micronucleus assay (RSMN assay): 72h protocol

Three compounds with nitrocarbazole frameworks were synthesized and their electrochemical reversibility as organic electrocatalysts was studied by cyclic voltammetry. The electrochemical reversibility and oxidation-reduction potential of the compounds were greatly affected by their substituents. The oxidation-reduction potential of the compound with an electron-donating group was negative, while that of the compound with an electron-withdrawing group on the carbazole framework was positive. The electrocatalytic oxidation activities of the nitrocarbazole compounds were investigated through cyclic voltammetry and controlled potential electrolysis at room temperature. The electrocatalysts showed excellent selectivity for p-methoxybenzyl alcohol, converting it to the corresponding aldehyde through electro-oxidation with just 2.5 mol% of the electrocatalysts presented. The electrocatalysts maintained their excellent electroredox activity following recycling.

Synthesis of nitrocarbazole compounds and their electrocatalytic oxidation of alcohol

Three compounds with nitrocarbazole frameworks were synthesized and their electrochemical reversibility as organic electrocatalysts was studied by cyclic voltammetry. The electrochemical reversibility and oxidation-reduction potential of the compounds were greatly affected by their substituents. The oxidation-reduction potential of the compound with an electron-donating group was negative, while that of the compound with an electron-withdrawing group on the carbazole framework was positive. The electrocatalytic oxidation activities of the nitrocarbazole compounds were investigated through cyclic voltammetry and controlled potential electrolysis at room temperature. The electrocatalysts showed excellent selectivity for p-methoxybenzyl alcohol, converting it to the corresponding aldehyde through electro-oxidation with just 2.5 mol% of the electrocatalysts presented. The electrocatalysts maintained their excellent electroredox activity following recycling.

Access to Substituted Carbazoles in Water by a One‐Pot Sequential Reaction of α,β‐Substituted Nitro Olefins with 2‐(3‐Formyl‐1H‐indol‐2‐yl)acetates

AbstractA series of interesting new multifunctional carbazole scaffolds have been prepared in good to excellent yields by an organocatalytic one‐pot two‐step sequential reaction between α‐alkyl‐β‐substituted nitro olefins or α‐alkyl‐δ‐substituted nitro‐dienes and 2‐(3‐formyl‐1H‐indol‐2‐yl)acetates in water at room temperature followed by treatment with 2 n HCl under mild conditions. This one‐pot, organocatalytic, oxidant‐free, mild, and eco‐friendly process may provide a powerful alternative synthetic protocol to rapidly access 3‐alkyl‐substituted carbazole frameworks that have a close structural resemblance to biologically active natural carbazoles. Moreover, biologically significant cyclic imide‐ and quinolinone‐fused carbazoles have been efficiently prepared by using this synthetic method.

Total syntheses of murrayamine E, I, and K.

We describe efficient synthetic routes to murrayamine A (mukoenine C), O-methylmurrayamine A, mahanine, O-methylmahanine, and murrayamine D and the first total syntheses of murrayamine E, I, and K. Key steps are a palladium-catalyzed construction of the carbazole framework and an annulation of the pyran ring, which is either catalyzed by phenylboronic acid or promoted by a Lewis acid.

Total synthesis of glycomaurrol and eustifoline-C by DIBAL-H promoted reductive ring opening of pyrano[2,3-c]carbazoles

The palladium-catalyzed construction of the carbazole framework provides an efficient access to 3-hydroxy-6-methylcarbazole (glycozolinine) (5). Regioselective annulation of a pyran ring at glycozolinine (5) using either a C5- or a C10-building block leads to the pyrano[2,3-c]carbazole alkaloids glycomaurin (5,6-pyranoglycozoline, eustifoline-A) (2) and eustifoline-B (4), respectively. Reductive opening of the pyran ring with DIBAL-H in the presence of an additional Lewis acid transformed 2 into the 5-prenyl-substituted carbazole alkaloid glycomaurrol (1) and 4 into the 5-geranyl-substituted homologue eustifoline-C (3).