Series Of Cyclopenta Research Articles

Cp*Co(III)-Catalyzed Regioselective Synthesis of Cyclopenta[ b]carbazoles via Dual C(sp2)-H Functionalization of 1-(Pyridin-2-yl)-indoles with Diynes.

Cp*Co(III)-catalyzed synthesis of cyclopenta[ b]carbazoles from 1-(pyridin-2-yl)-indoles and diynes is developed. This reaction involves dual C-H activation of indoles and domino cyclizations with diynes and has excellent regioselectivity, high efficiency, a broad substrate scope, and tolerance for various functional groups. A series of cyclopenta[ b]carbazole molecular scaffolds are obtained in good to excellent yields.

Chemodivergent Tandem Cyclizations of 2-Indolylmethanols with Tryptophols: C-N versus C-C Bond Formation.

A chemodivergent reaction of 2-indolylmethanols with tryptophols has been established via an interrupted Nazarov-type cyclization in the presence of Brønsted acid, leading to the efficient synthesis of two series of cyclopenta[ b]indole derivatives in a broad substrate scope with high yields and excellent diastereoselectivities (42 examples, up to 99% yield, all >95:5 dr). It was found that the presence or absence of molecular sieves played an important role in controlling the chemoselectivity of the reaction. In the presence of 3 Å molecular sieves, tryptophol would utilize the nucleophilicity of its nitrogen atom to form a new C-N bond, while, in the absence of molecular sieves, tryptophol would utilize the nucleophilicity of its C2-position to generate a new C-C bond. Therefore, this reaction will provide a good example for additive-controlled chemoselectivity. In addition, this approach not only provides a useful strategy for the synthesis of structurally diversified cyclopenta[ b]indoles but also demonstrates the practicability of 2-indolylmethanols in organic synthesis.

Synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of cyclopenta(hepta)[b]thiophene and fused cyclohepta[b]thiophene analogs

New series of cyclopenta(hepta)[b]thiophene and fused cyclohepta[b]thiophene analogs were synthesized. The new analogs were assessed for antibacterial efficacy toward Escherichia coli ATCC 12435, Bacillus cereus UW 85 and Staphylococcus aureus. Compounds 5a, 6b and 12 showed eminent activity toward all selected bacterial strains compared to ampicillin. The antifungal efficacy of the same analogs was also examined toward Candida albicans and Aspergillus fumigatus 293, whereas 5a,b and 12 showed excellent efficacy toward both of the tested fungi. Moreover, 4b, 6a, 14a and 17 demonstrated interesting antifungal efficacy toward A. fumigatus. The same analogs were assessed for antiquorum-sensing efficacy toward Chromobacterium violacium ATCC 12472, whereas 5a, 12 and 15a demonstrated moderate activity. The new analogs were also esteemed for in vitro antitumor activity over HepG2, MCF-7 and HT-29 cancer cell lines. Results indicated that 6b and 10 are the most potent analogs against the three tested cell lines. In addition, 5a, 6a, 7 and 15a displayed interesting activity toward all tested cell lines. The active in vitro antitumor analogs were screened for in vivo antitumor activity over EAC in mice as well as in vitro cytotoxicity toward W138 human normal cell line. Results demonstrated that 6a,b and 10 have the highest in vivo activity, and that all tested compounds were found to be less cytotoxic than 5-FU toward W138 normal cell line. The DNA-binding affinity of the active antimicrobial and/or antitumor analogs was also assessed, whereas 4a, 5b, 10 and 15a exhibited the highest affinity. In silico studies affirmed that the inspected compounds are compatible with Lipinski's rule of five with expected good oral absorption.

Synthesis of annulated pyridines as inhibitors of aldosterone synthase (CYP11B2).

A series of cyclopenta[c]pyridine aldosterone synthase (AS) inhibitors were conveniently accessed using batch or continuous flow Kondrat'eva reactions. Preparation of the analogous cyclohexa[c]pyridines led to the identification of a potent and more selective AS inhibitor. The structure-activity-relationship (SAR) in this new series was rationalized using binding mode models in the crystal structure of AS.

Facile synthesis and antimicrobial activity of a novel series of 7,8-dihydro-2-(2-oxo-2H-chromen-3-yl)-5-aryl-cyclopenta[b]pyrano-pyrimidine-4,6-5H-dione derivatives catalyzed by reusable silica-bonded N-propyl diethylenetriamine sulfamic acid

An efficient method for the synthesis of a novel series of cyclopenta[b]pyrano pyrimidinone derivatives with silica-bonded N-propyl diethylenetriamine sulfamic acid (SBPDSA) as catalyst has been achieved by the condensation of 2-amino-4-phenyl-5-oxo-4,5,6,7-tetrahydrocyclopenta[b]pyran-3-carbonitrile derivatives and coumarin-3-carboxylic acid under solvent free conditions. Antimicrobial studies showed all the target compounds processing good antibacterial and antifungal activities.

The discovery and SAR of cyclopenta[b]furans as inhibitors of CCR2

The discovery of a novel series of cyclopenta[b]furans as CCR2 inhibitors is discussed. This series has excellent CCR2 potency and PK characteristics, and good cardiovascular safety.

Study of regioselectivity of reactions between 3(5)-aminopyrazoles and 2-acetylcycloalkanones

Regioselectivity was examined of reactions between nine 3(5)-aminopyrazoles and 2-acetylcyclopentanone and 2-acetylcyclohexanone under various conditions. A series of cyclopenta[e]pyrazolo-[1,5-a]pyrimidines was obtained. The highest regioselectivity of the reaction was observed in alcohol at 20°C in the presence of a catalytic quantity of trifl uoroacetic acid. The regiostructure of compounds was established by 1H and 13C NMR spectroscopy.

Thiophenium-ylides: Synthesis and reactivity

AbstractThe reaction of propanedioic acid, 2-diazo-1,3-bis(1,1-dimethylethyl) ester (di-tert-butyl diazomalonate) with a series of cyclopenta[b]thiophenes in the presence of catalytic rhodium acetate was studied. The resulting S—C ylides underwent a rearrangement to form a heterocycle with different topology; thialene, in very low yields. Experimental and spectral data for all compounds are provided.

A Green Method for the Synthesis of Cyclopenta[b]chromen‐1(9H)‐one Derivatives in Ionic Liquids

AbstractA series of cyclopenta[b]chromen‐1(9H)‐one derivatives is prepared in high yields by a one‐pot reaction of substituted salicylaldehydes and cyclopentane‐1,3‐dione in ionic liquids of [BMIm]Br, the procedure is very mild and environmentally benign.

ChemInform Abstract: Stable Ion Study of Protonated Cyclopenta[a]phenanthrenes. Structure-Reactivity Relationships and Charge Delocalization in the Carbocations.

Protonation studies are reported for a series of cyclopenta[a]phenanthrenes Cp[a]P in superacid media. Hydrocarbons 1, 4, 7, are ring protonated in FSO3H–SO2ClF to form monoarenium ions. The Δcompounds 3, 6 are protonated at the D-ring double-bond to form stable α-phenanthrene-substituted carbocations. The 17-keto derivatives 2, 5, 8, 9, 19, 20 are CO-protonated in FSO3H–SO2ClF to form carboxonium ions. Carboxonium ions derived from 8 and 20 undergo ring fluorosulfonation in the biologically important A-ring under thermodynamic control (higher temperatures and prolonged reaction times). Low temperature protonation of 8 and 9 with FSO3H·SbF5 (4∶1)–SO2ClF gives their corresponding carboxonium-arenium dications (protonation of 2 with FSO3H·SbF5 (1∶1)–SO2ClF gave a mixture of mono- and dications), where ring protonation sites are controlled by the position of the methyl group and occur in the A-ring for the A-ring methylated derivatives (8, 9). Whereas the 11-methoxy derivative (16) forms a carboxonium ion in FSO3H–SO2ClF analogous to the 11-Me derivative (5), the 11-phenol derivative (15), the ethoxy (17) and propoxy (18) derivatives are more reactive, forming a mixture of mono- and dication (with 15 and 17) or give mostly a carboxonium-arenium dication (with 18). Substituent effects observed under stable ion conditions emphasize relative carbocation stability and relief of peri-strain. Under thermodynamic control, carboxonium ions undergo fluorosulfonation in the biologically important A-ring. Charge delocalizations in the resulting mono- and dications (deduced primarily based on magnitude of Δδ13C) are discussed and compared. In an effort to further enhance the NMR assignments and for comparison, mono-arenium ions 1H++, 4H++, 6H++, 7H++ and their neutral precursors were calculated at the B3LYP/6-31G(d,p) level of ab initio theory; their 1H and 13C NMR chemical shifts were computed by the GIAO method and their overall charge delocalization paths were deduced via differences in the NPA charges (cation minus neutral). The results are compared and discussed. Stable ion studies of CP[a]P provide useful insights into the contrasting regioselectivities observed in chemical and biological activiation. p

Stable ion study of protonated cyclopenta[a]phenanthrenes. Structure–reactivity relationships and charge delocalization in the carbocations †

Protonation studies are reported for a series of cyclopenta[a]phenanthrenes Cp[a]P in superacid media. Hydrocarbons 1, 4, 7, are ring protonated in FSO3H–SO2ClF to form monoarenium ions. The Δcompounds 3, 6 are protonated at the D-ring double-bond to form stable α-phenanthrene-substituted carbocations. The 17-keto derivatives 2, 5, 8, 9, 19, 20 are CO-protonated in FSO3H–SO2ClF to form carboxonium ions. Carboxonium ions derived from 8 and 20 undergo ring fluorosulfonation in the biologically important A-ring under thermodynamic control (higher temperatures and prolonged reaction times). Low temperature protonation of 8 and 9 with FSO3H·SbF5 (4∶1)–SO2ClF gives their corresponding carboxonium-arenium dications (protonation of 2 with FSO3H·SbF5 (1∶1)–SO2ClF gave a mixture of mono- and dications), where ring protonation sites are controlled by the position of the methyl group and occur in the A-ring for the A-ring methylated derivatives (8, 9). Whereas the 11-methoxy derivative (16) forms a carboxonium ion in FSO3H–SO2ClF analogous to the 11-Me derivative (5), the 11-phenol derivative (15), the ethoxy (17) and propoxy (18) derivatives are more reactive, forming a mixture of mono- and dication (with 15 and 17) or give mostly a carboxonium-arenium dication (with 18). Substituent effects observed under stable ion conditions emphasize relative carbocation stability and relief of peri-strain. Under thermodynamic control, carboxonium ions undergo fluorosulfonation in the biologically important A-ring. Charge delocalizations in the resulting mono- and dications (deduced primarily based on magnitude of Δδ13C) are discussed and compared. In an effort to further enhance the NMR assignments and for comparison, mono-arenium ions 1H++, 4H++, 6H++, 7H++ and their neutral precursors were calculated at the B3LYP/6-31G(d,p) level of ab initio theory; their 1H and 13C NMR chemical shifts were computed by the GIAO method and their overall charge delocalization paths were deduced via differences in the NPA charges (cation minus neutral). The results are compared and discussed. Stable ion studies of CP[a]P provide useful insights into the contrasting regioselectivities observed in chemical and biological activiation. p