Pentacyclic System Research Articles

Roquefornine A, a sesterterpenoid with a 5/6/5/5/6-fused ring system from the fungus Penicillium roqueforti YJ-14

Roquefornine A, a sesterterpenoid with an unprecedented 5/6/5/5/6-membered pentacyclic system, was characterized from Penicillium roqueforti YJ-14.

Ganorbifates A and B from Ganoderma orbiforme, determined by DFT calculations of NMR data and ECD spectra

Ganorbifate A featuring an unprecedented 6/6/6/5/5 pentacyclic system, and ganorbifate B with an unusual 6/4/6/5/8/5 ring system were isolated from the fruiting body of Ganoderma orbiforme. Their structures were established using extensive spectroscopic analysis, including DFT calculations of NMR data and ECD spectra.

3-Bromofascaplysin is a prospective chemical compound for developing new chemotherapy agents in glioblastoma treatment.

The study used rat glioma C6 cell line (ATCC®; cat no CCL-107), U-87MG cell line (ATCC; cat no. HTB-14™) and human glioblastoma T98-G cells (ATCC® CRL-1690™). Cell culture method, experimental pharmacological trials and γ-radiation in vitro, as well as flow cytofluorometry were used in the study. Cytotoxic effect of the tested compounds is stronger than the effect of unsubstituted fascaplysin, and appears to be dose-dependent and time-dependent. 3-bromofascaplysin is more efficient for cancer cells elimination, and by the end of the experiment the amount of living cancer cells in G0 phase remained at its lowest. Cytotoxic effect of 3-bromofascaplysin on glioblastoma T98-G cells is inferior to that of TMZ, and in case of preliminary radiation treatment of cancer cells with 48Gy the effect of the compound matches the TMZ treatment results. 3-Bromofascaplysin is a prospective chemical compound for development of new anti-cancer chemotherapeutic agents.

One pot synthesis of ethyl carboxylate and acetyl selenolo[2,3-b]quinoline derivatives and their tetra/pentacyclic systems

Ethylcarboxylate and acetyl selenoloquinoline derivatives were prepared in a one pot synthesis via reaction of sodium hydrogen selenide and 2-chloro-3-cyano-4-methylquinoline followed by reactions with ethyl chloroacetate and chloro acetone respectively which used as precursors to synthesize many of tetra and pentacyclic systems. A new series of pyrimido [4′,5′:4,5]selenolo[2,3-b]quinoline, thiazino[2’,3’:4,5]selenolo[2,3-b]quinoline, oxazino[2',3':4,5]selenolo[3,2-b]quinoline, pyrido[2′,3′:4,5]selenolo[2,3-b]quinoline, pyrido[2′,3′:4,5]selenolo[2,3-b]quinoline-2-substituted selenyl and selenolo[2′,3′:5,6]pyrido[2″,3″:4,5]selenolo[2,3-b]quinoline derivatives were prepared. Elemental analysis, IR, 1H NMR, 13C NMR and mass spectra confirmed the structures of the newly synthesized compounds.

DMOA-based meroterpenoids with diverse scaffolds from the sponge-associated fungus Penicillium brasilianum

Bioinformatics analysis of the synthetic gene clusters in association with the qRT-PCR detection led to speculate a marine derived fungus, Penicillium brasilianum WZXY-m122-9, to be potential to produce meroterpenoids. Chromatographic separation of the EtOAc extract of this fungal strain on a large-scale fermentation resulted in the isolation of six new DMOA-related meroterpenoids, namely brasilianoids G‒L (1–6), together with nine known meroterpenes. Their structures were determined by extensive analyses of spectroscopic data, including the X-ray diffraction and the ECD data for configurational assignment. Brasilianoid G is characterized by the presence of an unprecedented scaffold bearing a 6/6/5/5/5 pentacyclic nucleus, while brasilianoid K possessing a 7/6/6/6/5 pentacyclic system is uncommonly found from nature. The biogenetic relationship among the isolated compounds was postulated based on the comparative analyses of gene clusters. Brasilianoid L (6), austinol (12), and dehydroaustin (14) exhibited significant inhibition against bacteria invasion into host cells, that was suggested to be mediated by preventing the polymerization of actin in the host cells.

Direct Synthesis of Polycyclic Tropinones by a Condensation-[4+3]-Cycloaddition Cascade Reaction.

A concise method of constructing polycyclic tropinone frameworks was developed. The single-step synthesis of polycyclic tropinone consists of an intramolecular [4+3] cycloaddition reaction of N-nosyl-pyrrole with oxyallyl cation that was generated in situ by an intermolecular condensation reaction of the nucleophilic functional groups on a tethered pyrrole with the aldehyde of 2-(silyloxy)-acrolein. This cascade reaction afforded various polycyclic tropinones including tri-, tetra-, and pentacyclic systems in high yields as single diastereomers.

Fluvirosaones A and B, Two Indolizidine Alkaloids with a Pentacyclic Skeleton from Flueggea virosa.

Fluvirosaones A (1) and B (2), together with virosecurinine (3), were isolated from Flueggea virosa. Their structures were determined by physical, spectroscopic, and X-ray analysis and confirmed through comparison of the calculated and experimental 13C NMR and electronic circular dichroism (ECD) data. Compounds 1 and 2 represent the first examples of a pentacyclic Securinega alkaloid containing a pentacyclic system and an α,β-unsaturated ketone. Plausible biogenetic pathways of compounds 1 and 2 are proposed.

Pentacyclic Triterpenoids from Maytenus cuzcoina

Phytochemical analysis of the root bark extract of Maytenus cuzcoina (Celastraceae) led to the isolation and characterization of sixteen triterpenoids with a 6/6/6/6/6 pentacyclic system, including the new 22α-hydroxy-29-methoxy-3β-tetradecanoate-olean-12-ene, and 3β,24β-epoxy-29-methoxy-2α,3α,6α- -trihydroxy-D:A-friedelane that is reported for the first time as a natural product. This is the first instance of the isolation of a tetradecanoate triterpene ester from a Celastraceae species. The structures were elucidated on the basis of spectrometric and spectroscopic methods, including ID and 2D NMR techniques.

Design and Synthesis Pairing Between Xanthene and Tetrazole in Pentacyclic System Using Tetrachlorosilane with Aurora Kinase Inhibitor Validation

A competent new one‐pot synthesis for tetrahydrobenzo[f]chromeno[3,2‐c]tetrazolo[1,5‐a]azepines through the catalytic synthesis of related xanthenes. β‐naphthol, dimedone, aromatic aldehydes were stirred under solvent free condition in the presence of tetrachlorosilane (TCS), then azidochlorosilane (which prepared in situ from sodium azide and TCS in acetonitrile as solvent) was added and the reaction was stirred at 50‐60 oC. A molecular docking of the synthesized compounds was carried out in order to investigate their binding pattern with the prospective target Aurora kinase all the synthesized molecules gave strong interaction with protein pocket residues and low energy score (−6.99 to −6.52 kcal/mol and rmsd < 1.5) compared with AKI‐001 reference molecule (−5.87 kcal/mol and rmsd = 0.90). (PDB‐ID: 3COH)

Novel Diazole/Triazole and Dibenzothiophene Dioxide Containing Pentacyclic Systems with Promising Biological Activities

The aim of the current work is to synthesize the new heterocyclic pentacyclic condensed systems that combine benzothiophen and benzimidazole/triazole into one molecule. The dibenzothiophene was taken as an initial compound and by consistent “extension” was annihilated the imidazole and triazole nucleuses. As a result two new pentacyclic systems were produced: 3H-, 7H-diimidazole[4,5-b][5,4-g] dibenzothiophene-5,5-dioxide and 3H-, 7H-ditriazole[4,5-b][5,4-g] dibenzothiophene-5,5-dioxide with the promising antimi-crobial activity. Their spectral characteristics were studied.

Glycyrrhetinic acid and its derivatives in infectious diseases

AbstractIntroduction.Licorice or liquorice (Glycyrrhiza glabra, Leguminosae) is a perennial plant naturally occurring or cultivated in Europe and Asia. It was appreciated by many ancient cultures, and was employed within Arabic medicine and (beginning in the Middle Ages) in Europe folk medicine as a remedy for many diseases. Currently, the sweet flavoured root of this plant – Radix Glycyrrhizae (Liquirtiae), is widely taken for the treating of various upper respiratory tract diseases, as well as for gastric ulcer disease. It is also utilized as a sweetening and flavouring agent in the food, tobacco and pharmacy industries. The main active ingredient of liquorice is the triterpenoid saponin, glycyrrhizin, which is a mixture of calcium, magnesium and potassium salts of glycyrrhizic acid (GA). Glycyrrhizic acid is composed of an aglycone, that is 18β-glycyrrhetinic acid (GE), and a D-glucuronic acid dimer. The aim of this review is to discuss some aspects of the activity of glycyrrhetinic acid and its derivatives in infectious diseases.State of knowledge.The pentacyclic system of glycyrrhetinic acid consists of condensed six-membered rings with a hydroxyl group at C-3, a carboxyl moiety at C-30 and a ketone functional group at C-11. Considering the presence of the above mentioned functional groups, many structural transformations have been proposed, including those by way of esterification, alkylation and reduction reactions. The introduction of various chemical residues into its structure, as well as the modification of the glycyrrhetinic acid in its pentacyclic triterpene skeleton, has led to the generation of compounds with many valuable antimicrobial, anti-parasitic, antiviral properties and modified lipophilic parameters.Summary.In summary, glycyrrhetinic acid derivatives appear to have promise as active pharmaceutical ingredients that contain a wide range of biological and pharmacological properties.

ChemInform Abstract: Symmetry‐Driven Strategy for the Assembly of the Core Tetracycle of (+)‐Ryanodine: Synthetic Utility of a Cobalt‐Catalyzed Olefin Oxidation and α‐Alkoxy Bridgehead Radical Reaction.

Ryanodine (1) is a potent modulator of intracellular calcium release channels, designated as ryanodine receptors. The exceptionally complex molecular architecture of 1 comprises a highly oxygenated pentacyclic system with eleven contiguous stereogenic centers, which makes it a formidable target for organic synthesis. We identified the embedded C2 -symmetric tricyclic substructure within 1. This specific recognition permitted us to design a concise synthetic route to enantiopure tricycle 9 by utilizing a series of pairwise functionalizations. The four tetrasubstituted carbon centers of 9 were effectively constructed by three key reactions, a dearomatizing Diels-Alder reaction, the kinetic resolution of the obtained racemic 14 through asymmetric methanolysis, and the transannular aldol reaction of the eight-membered diketone 10. A new combination of cobalt-catalyzed hydroperoxidation and NfF-promoted elimination enabled conversion of the hindered olefin of 9 into the corresponding ketone, thus realizing the desymmetrization. Finally, the tetrasubstituted carbon was stereospecifically installed by utilizing the α-alkoxy bridgehead radical to deliver the core tetracycle 7 with the six contiguous tetrasubstituted carbon centers. Consequently, the present work not only accomplishes efficient assembly of four out of the five fused rings of 1, but also develops two new powerful methodologies: two-step ketone formation and bridgehead radical reaction.

Symmetry-Driven Strategy for the Assembly of the Core Tetracycle of (+)-Ryanodine: Synthetic Utility of a Cobalt-Catalyzed Olefin Oxidation and α-Alkoxy Bridgehead Radical Reaction.

Ryanodine (1) is a potent modulator of intracellular calcium release channels, designated as ryanodine receptors. The exceptionally complex molecular architecture of 1 comprises a highly oxygenated pentacyclic system with eleven contiguous stereogenic centers, which makes it a formidable target for organic synthesis. We identified the embedded C2 -symmetric tricyclic substructure within 1. This specific recognition permitted us to design a concise synthetic route to enantiopure tricycle 9 by utilizing a series of pairwise functionalizations. The four tetrasubstituted carbon centers of 9 were effectively constructed by three key reactions, a dearomatizing Diels-Alder reaction, the kinetic resolution of the obtained racemic 14 through asymmetric methanolysis, and the transannular aldol reaction of the eight-membered diketone 10. A new combination of cobalt-catalyzed hydroperoxidation and NfF-promoted elimination enabled conversion of the hindered olefin of 9 into the corresponding ketone, thus realizing the desymmetrization. Finally, the tetrasubstituted carbon was stereospecifically installed by utilizing the α-alkoxy bridgehead radical to deliver the core tetracycle 7 with the six contiguous tetrasubstituted carbon centers. Consequently, the present work not only accomplishes efficient assembly of four out of the five fused rings of 1, but also develops two new powerful methodologies: two-step ketone formation and bridgehead radical reaction.

On the reactivity of pyrido[3′,2′:4,5]furo(thieno)[3,2-d]pyrimidin-7(8)-ones with some alkyl mono- and di-halides: synthesis of new heterocyclic systems containing thiazolo[3,2-a]pyrimidine and pyrimido[2,1-b]thiazine moiety

Ethyl 1-aminofuro(thieno)[2,3-b]pyridine-2-carboxylates 1 reacted with benzoyl isothiocyanate and gave the relevant thioureido derivatives 2, whose intramolecular cyclization under the action of potassium hydroxide furnished the relevant 9(10)-thioxopyrido[3′,2′:4,5]furo(thieno)[3,2-d]pyrimidin-7(8)-ones 3. Compounds 3 with methyl iodide could give the S-methyl 4 and S,N-dimethyl 5 derivatives. Interestingly 3 by alkylation with alkyl dichlorides (bifunctional reagents) the cyclization to a thiazoline or to a thiazine ring on the [a] side of the pyrimidine ring occurs, with formation of the new pentacyclic systems: furo(thieno)[3,2-d][1,3]thiazolo[3,2-a]pyrimidin-7(8)-ones 6 and furo(thieno)[3′,2′:4,5]pyrimido[2,1-b][1,3]thiazin-7(8)-ones 7. Moreover compounds 3 by alkylation with p-chlorophenacyl bromide (again a bifunctional reagent) led to the formation of the corresponding S-alkylated compounds 9, whose cyclization furnished structural analogues of compounds 6: p-chlorophenyl-substituted thiazolo[3,2-a]pyrimidin-7(8)-ones 10. The structure of the obtained compounds has been unambiguously confirmed by using a wide spectrum of physico-chemical methods and, in the instance of compounds 6 and 7, also by an alternative synthesis via a double-annelation reaction using a BMMA reagent. Biological tests have shown promising antimicrobial activity against Staphylococcus aureus for some of the synthesized compounds.

Enantioselective total synthesis of the lignan (+)-linoxepin.

An enantioselective total synthesis of the natural (+)-linoxepin (1) was accomplished in eleven steps from bromovanin (24). Key steps are a domino carbopalladation/ Mizoroki-Heck reaction with the formation of a pentacyclic system, an asymmetric hydroboration as well as an oxidative lactonization.

ChemInform Abstract: General Approach to Spiroacenaphthylene Pentacyclic Systems: Direct Multicomponent Assembling of Acenaphthenequinone and Cyclic Carbonyl Compounds with Two Molecules of Malononitrile.

Abstract A new type of catalytic cascade reaction was found: the direct multicomponent transformation of acenaphthenequinone, cyclic ketones, and two molecules of malononitrile into spiroacenaphthylene pentacyclic systems. The fast (5 min) reaction of acenaphthenequinone, cyclic ketones, and 2 equiv of malononitrile at ambient temperature results in the formation of pentacyclic and pentaheterocyclic spiroacenaphthylene frameworks in 70–95% yields. Thus, a new simple fast and efficient ‘one-pot’ method to synthesize substituted spiroacenaphthylene frameworks was found directly from simple starting compounds. The application of this convenient multicomponent method is also beneficial from the viewpoint of diversity-oriented large-scale processes.

Synthesis, X-ray analysis and photophysical properties of a new N-containing pentacyclic helicene

A new helically chiral pentacyclic system containing one pyrrole ring was prepared in a good yield and purity via a three-step sequence involving Heck coupling and classical oxidative photocyclization. X-ray crystal structure analysis indicated that the conformation resembled that of unsubstituted pentahelicene, the idealized symmetry of which is C 2 . The optical properties of the pentacyclic helicene were investigated and show interesting behaviour.

Ethyl 4-(2-ethoxy-2-oxoethyl)-3-oxo-4,13-diazapentacyclo[11.8.0.02,11.05,10.014,19]henicosa-1,5(10),6,8,11,14(19),15,17,20-nonaene-12-carboxylate

In the title compound, C26H22N2O5, the system consisting of five fused rings, being essentially planar with an r.m.s. deviation from the least-squares plane of 0.049 (3) Å, makes a dihedral angle of 58.72 (12)° with the plane of the ethyl carboxyl­ate group immediately attached to it, and a dihedral angle of 89.48 (14)° with the plane of the ethyl carboxyl­ate group attached via the –CH2– bridge. Bond lengths indicate π-delocalization over the whole penta­cyclic system. The mol­ecular conformation is stabilized by a weak intra­molecular C—H⋯O hydrogen bond. In the crystal, mol­ecules form stacks along the b-axis direction, neighboring mol­ecules within each stack being related by inversion and the shortest distance between the centroids of the pyridine rings within the stack being 3.667 (2) Å.

General approach to spiroacenaphthylene pentacyclic systems: direct multicomponent assembling of acenaphthenequinone and cyclic carbonyl compounds with two molecules of malononitrile

A new type of catalytic cascade reaction was found: the direct multicomponent transformation of acenaphthenequinone, cyclic ketones, and two molecules of malononitrile into spiroacenaphthylene pentacyclic systems. The fast (5 min) reaction of acenaphthenequinone, cyclic ketones, and 2 equiv of malononitrile at ambient temperature results in the formation of pentacyclic and pentaheterocyclic spiroacenaphthylene frameworks in 70–95% yields. Thus, a new simple fast and efficient ‘one-pot’ method to synthesize substituted spiroacenaphthylene frameworks was found directly from simple starting compounds. The application of this convenient multicomponent method is also beneficial from the viewpoint of diversity-oriented large-scale processes.

Discovery of cationic domino reaction under the NMR experiment conditions: diastereoselective dimerization of 2-arylmethylideneindolin-3-ones to pentacyclic 3-hydroxyindolenine system

NMR spectroscopy (1D and 2D) showed that the protonation of the capto-dative heterocyclic α-amino enones, viz., (Z)-2-arylmethylideneindolin-3-ones, with strong acids led to stable (aryl)(3-hydroxyindol-2-yl)methyl cations. These substrates in trifluoroacetic acid underwent cationic domino reaction, which resulted in polynuclear pyrido[1,2-a: 5,6-b′]-[1,2′]biindoles.