Eight-membered Ring Compounds Research Articles

Synthesis and Characterization of an Eight-Membered Heterocyclic 1,3,5,7-Tetra(3-pyridyl)-1,3,5,7-tetrazacyclooctane

Abstract N,N′-Bis(3-pyridyl)methanediamine was prepared by treating 3-aminopyridine with formaldehyde in acetonitrile. By treating it with formaldehyde, the eight-membered heterocyclic ring compound 1,3,5,7-tetra(3-pyridyl)-1,3,5,7-tetrazacyclooctane was prepared. This could occur in a two-step manner in a [3+1+3+1] cycloaddition reaction. The compounds were characterized by X-ray crystallography, 1H and 13C NMR spectroscopy, and mass spectrometry. The powder XRD pattern of 1,3,5,7-tetra(3-pyridyl)-1,3,5,7-tetrazacyclooctane was also determined and revealed an uncommon twist-crown conformation, which was further confirmed by DFT calculations.

A Cysteine-Reloading Process Initiating the Biosynthesis of the Bicyclic Scaffold of Dithiolopyrrolones.

Dithiolopyrrolone antibiotics are well known for their outstanding biological activities, and their biosynthesis has been studied vigorously. However, the biosynthesis mechanism of the characteristic bicyclic scaffold is still unknown after years of research. To uncover this mechanism, a multi-domain non-ribosomal peptide synthase DtpB from the biosynthetic gene cluster of thiolutin was selected as an object to study. We discovered that its adenylation domain not only recognized and adenylated cysteine, but also played an essential role in the formation of the peptide bond. Notably, an eight-membered ring compound was also discovered as an intermediate during the formation of the bicyclic structure. Based on these findings, we propose a new mechanism for the biosynthesis of the bicyclic scaffold of dithiolopyrrolones, and unveil additional functions of the adenylation domain.

Theoretical insight into electronic and molecular properties of halogenated (F, Cl, Br) and hetero-atom (N, O, S) doped cyclooctane

Undoubtedly, cyclooctane has been investigated theoretically and experimentally, however, considering the vast application of cycloalkanes and limited research for the higher members, the reactivity and structural investigation of cyclooctane, fluorocyclooctane, bromocyclooctane, chlorocyclooctane, azocane, oxocane and thiocane have been explored using density functional theory (DFT) method. In this work, we reported elaborately on some molecular and electronic properties. Interestingly, the condensed dual descriptors (Δf); Br24 of bromocyclooctane compound and N22 of azocane compound has the highest positive values of 0.3561eV and 0.1618eV respectively and hence, potential sites for nucleophilic reaction compared to chlorocyclooctane, fluorocyclooctane, oxocane, thiocane and the parent cyclooctane. In the UV-VIS spectroscopic analysis, σ-π* nor π to π* transitions where observed for all the studied molecules and these molecules are expected to be colorless due to the absence of an absorption band in the visible region (380–760 nm). In all the substituted cyclooctane molecules investigated, C–F bond of fluorocyclooctane is more polar than C–O, C–S, C–N, C–Cl, C–Br bonds of other compounds. The interactions between the lone pair (LP (1) N22) and antibonding; σ*(1)C4–C5 of azocane gave the highest stabilization energy (10.44 kcal/mol) compared to other compounds investigated. We believe our detail reported work on this eight-membered ring compound and its derivatives will widen the scope of these molecules to other researchers.

Heterocyclic organobismuth (III) compounds containing an eight-membered ring: Inhibitory effects on cell cycle progression

We previously showed that heterocyclic organobismuth compounds have excellent antimicrobial and antitumor potential. These compounds structurally consist of either six- or eight-membered rings. Previous research has shown that bi-chlorodibenzo[c,f][1,5]thiabismocine (Compound 3), an eight-membered ring, induced G2/M arrest via inhibition of tubulin polymerization in HeLa cells. Additionally, N-tert-butyl-bi-chlorodi-benzo[c,f][1,5]azabismocine (Compound 1), another eight-membered ring, exhibited higher cytotoxicity than Compound 3 against several cancer cell lines, including HeLa and K562. Finally, bi-chlorophenothiabismin-S,S-dioxide (Compound 5), a six-membered ring, exhibited lower antitumor activity than eight-membered ring compounds. In this study, we investigated the antimitotic activity of Compounds 1 and 5 in HeLa cells. At low concentrations, (0.1 and 0.25 μM), Compound 1 inhibited cell growth and arrested the cell cycle in mitosis. However, 0.5 μM Compound 1 exhibited no antimitotic activity. Conversely, Compound 5 weakly inhibited cell growth and did not markedly arrest the cell cycle. Flow cytometry showed that Compound 1 arrested the cell cycle at G2/M, resulting in apoptosis. Compound 1 inhibited tubulin polymerization as revealed by a cell-free assay, and both Compounds 1 and 3 inhibited microtubule spindle formation and chromosome alignment during prometaphase. These results suggest that eight-membered ring-containing organobismuth compounds can induce mitotic arrest by perturbing spindle dynamics.

Our expedition in eight-membered ring compounds: from planar dehydrocyclooctenes to tub-shaped chiral tetraphenylenes.

Our research focus for almost forty years concerning eight-membered ring compounds is herein summarized. The design and preparation of these structurally unique compounds featuring a central cyclooctene ring are described in the context of their planar or tub-shaped conformations. Furthermore, their intrinsic properties and potential applications are also presented.

Transition-Metal Catalysis with Hollow-Shaped Triethynylphosphine Ligands

Abstract Triethynylphosphines with bulky end caps such as triarylsilyl and triarylmethyl groups at alkyne termini have a novel molecular shape presenting a large, deep metal-binding cavity. The hollow-shaped triethynylphosphines functioned as effective ligands in the rhodium-catalyzed hydrosilylation of ketones with triorganosilanes due to the preferential formation of a mono-P-ligated rhodium species. Furthermore, the phosphines displayed remarkable rate enhancement in the gold(I)-catalyzed alkyne cyclization constructing six- to eight-membered ring compounds. It is proposed that the cavity in the ligand forces a nucleophilic center of the acetylenic compounds close to the gold-bound alkyne, making ring-closing anti attack feasible.

ChemInform Abstract: (4 + 4) Cycloaddition Reactions in the Total Synthesis of Naturally Occurring Eight-Membered Ring Compounds

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ChemInform Abstract: Compounds with Larger Heterocyclic Rings: Eight-Membered Ring Compounds

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Synthesis of Eight-Membered Ring Compounds Using Enyne Metathesis.

A novel procedure for synthesizing eight-membered ring compounds was developed using ruthenium-catalyzed enyne metathesis. When a CH2Cl2 solution of enyne connected with catechol, o-amino phenol, or o-phenylenediamine was stirred in the presence of benzylidene ruthenium carbene complex (10 mol %) at room temperature overnight, an eight-membered ring compound was obtained in high yield. In a similar manner, monocyclic 1,4-diaza- or 1-oxa-4-azacyclooctene derivative was obtained in high yield.

Density functional theory study of piperidine and diazocine compounds

Density functional theory calculations at the B3LYP/6-311G** level were performed to predict the heats of formation (HOFs) for three eight-membered ring compounds and four six-membered ring compounds via designed isodesmic reactions. In the isodesmic reactions designed for the computation of HOFs (CH 3CH 2) 2NNO 2 and piperidine were chosen as reference compounds. The HOFs for −NO 2 substituted derivations are larger than those of −NF 2 substituent groups. Thermal stability were evaluated via bond dissociation energies (BDE) at the UB3LYP/6-311G** level. As a whole, the homolysis of C NF 2 or C NO 2 bonds is the main step for bond dissociation of the title compounds. Detonation properties of seven title compounds were evaluated by using the Kamlet–Jacobs equation based on the calculated densities and HOFs. It is found that 3,3,7,7-tetrakis(difluoroamino)octahydro-1,5-dinitro-1,5-diazocine (HNFX) and 3,3,5,5-tetrakis (difluoroamino)-1-nitro piperidine (N-nitro TDFAPP), with predicted density of ca. 2.0 g/cm 3, detonation velocity ( D) about 9.9 km/s, and detonation pressure ( P) of 47 GPa that are lager than those of HMX, are expected to be the novel candidates of high energy density materials (HEDMs). The detonation data of 1,3,3,5,7,7-hexanitro-1,5-diazacyclooctane (HNDZ) and TNBDFAPP show that they meet the requirements for HEDMs.

GaCl3-Catalyzed Formation of Eight-Membered Rings from Enynes Bearing a Cyclic Olefin

GaCl3-catalyzed cycloisomerization of enynes having a cyclic olefin led to isolation of eight-membered ring compounds. [reaction: see text].

Stereoselective Synthesis of Highly Enantioenriched (E)‐Allylsilanes by Palladium‐Catalyzed Intramolecular Bis‐Silylation: 1,3‐Chirality Transfer and Enantioenrichment via Dimer Formation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Planar Dehydro[8]annulenes and Their Ramifications: Substituted Tribenzo[a,c,e]cyclooctenes and Tetrabenzo[a,c,e,g]cyclooctenes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Alternative approaches towards glycosylated eight-membered ring compounds employing Claisen rearrangement of mono and disaccharide allyl vinyl ether precursors

Highly functionalized eight-membered rings having a glycosidic residue were synthesized in two different ways involving either glycosylation of a sugar-derived cyclooctenone with high stereocontrol as well as a Claisen rearrangement of a disaccharide derivative.

Planar Dehydro[8]annulenes and Their Ramifications: Substituted Tribenzo[a,c,e]cyclooctenes and Tetrabenzo[a,c,e,g]cyclooctenes

Our research endeavors on planar dehydro[8]annulenes were broadened into areas concerning syntheses and studies of strategically substituted tribenzo[a,c,e]cyclooctenes and tetrabenzo[a,c,e,g]cyclooctenes. Further conversion of these scaffolds led to novel molecules containing central planar eight-membered ring compounds.

Stereoselective Synthesis of Highly Enantioenriched (E)‐Allylsilanes by Palladium‐Catalyzed Intramolecular Bis‐Silylation: 1,3‐Chirality Transfer and Enantioenrichment via Dimer Formation

Highly enantioenriched (E)-allylsilanes have been synthesized from optically active allylic alcohols on the basis of Pd-catalyzed intramolecular bis-silylation followed by highly stereospecific Si-O elimination reactions. The method involves three steps: 1) O-disilanylation of the allylic alcohols with chlorodisilanes, 2) intramolecular bis-silylation in the presence of a 1,1,3,3-tetramethylbutyl isocyanide/[Pd(acac)2] (acac = acetylacetonate) catalyst at 110 degrees C, and 3) treatment of the reaction mixture with organolithium reagents. The overall transformation proceeds with nearly complete conservation of the enantiopurity of the starting allyl alcohols by transposition of the C=C bond. For instance, (R)-(E)-3-decen-2-ol (99.6-99.7 % ee) produced (S)-(E)-4-(organosilyl)-2-decene of 98.8-99.4 % ee for a variety of silyl groups, including Me3Si, Me2PhSi, tBuMe2Si, Et3Si, and iPr3Si. In the bis-silylation step, the initially formed trans-1,2-oxasiletanes immediately dimerize to stereoselectively give 1,5-dioxa-2,6-disilacyclooctanes, which are isolated in high yield by carrying out the reaction at 70 degrees C. The eight-membered ring compounds undergo thermal extrusion of (E)-allylsilanes in high yield at 110 degrees C, along with formation of 1,3-dioxa-2,5-disilacyclohexane derivatives. These in turn undergo a Peterson-type elimination by treatment with nucleophiles such as BuLi and PhLi to give the (E)-allylsilanes. All of the steps involved in the sequence proceed with extremely high stereoselectivity and stereospecificity, leading to almost complete 1,3-chirality transfer through the overall transformation. The dimerization step, which forms diastereomeric intermediates, allows the synthesis of a highly enantioenriched allylsilane (99.4 % ee) from an optically active allylic alcohol with lower enantiopurity (79.2 % ee) by enrichment of enantiopurity. A general method for the determination of the enantiomeric excesses of (E)-allylsilanes is also described in detail.

Regioselective Radical Ring‐Opening Reaction of Bicyclo[4.2.0]octan‐2‐ones Promoted by Samarium(II) Iodide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regioselective radical ring-opening reaction of bicyclo[4.2.0]octan-2-ones promoted by samarium(II) iodide

Radical ring-opening reactions of bicyclo[4.2.0]octanones, its C6 alkyl derivatives, and tricyclic ketones promoted by SmI 2 gave cyclohexanones via fission of the external cyclobutane bond. The CO 2Me, CN, and phenyl derivatives led to the production of the eight-membered ring compounds through cleavage of the central cyclobutane bond. Using this regioselective reaction, the synthesis of (±)-acorenone was achieved.

Five-, six- and eight-membered ring organosilicon chalcogenides of the types Z2(SiMe2)2E (Z = Me2Si, H2C; E = S, Se, Te), Z(SiMe2E)2MR2(Z = Me2Si, H2C, O; E = S, Se, Te; M = Si, Ge, Sn, R = Me, Ph) and (SiMe2ZSiMe2E)2(Z = Me2Si, H2C; E = S, Se)

Reactions of ClMe2Si–Z–SiMe2Cl (Z = SiMe2 (1a), CH2 (1c), O (1e)) with Li2E (E = S, Se) yielded eight-membered ring compounds (SiMe2ZSiMe2E)2 (3a–d) as well as acyclic oligomers (SiMe2ZSiMe2E)x of different chain lengths. If 1:1 molar mixtures of 1a, 1c or 1e and a diorganodichlorosilane, -germane or -stannane (R2MCl2) are reacted with Li2E (E = S, Se, Te), six-membered ring compounds Z(SiMe2E)2MR2 (4a–7g) are formed exclusively. Five-membered rings Z2(SiMe2)2E (Z = SiMe2 (8a–c), CH2 (9a–c); E = S, Se, Te) are obtained starting from the tetrasilane ClMe2Si–(SiMe2)2–SiMe2Cl (1b) or the disilylethane ClMe2Si–(CH2)2–SiMe2Cl (1d) by treatment with Li2E. All products were characterized by multinuclear NMR spectroscopy (1H, 13C, 29Si, 119Sn, 77Se, 125Te, including coupling constants) and the effects of the different ring sizes towards NMR chemical shifts are discussed.

A New and Convenient Method for the Preparation of Cyclooctanone Containing Bis-Aldol Skeleton by Samarium(II) Iodide-mediated Intramolecular Aldol Cyclization of ω-Oxiranyl Keto Octanal

Abstract A polyoxy eight-membered ring compound containing a bis-aldol skeleton, 2,6-dibenzyloxy-3-(t-butyldimethylsiloxy)-7-hydroxy-8-hydroxymethyl-5-(p-methoxybenzyloxy)-4,4-dimethylcyclooctanone 1, a key synthetic intermediate of 19-hydroxypaclitaxel, was prepared in high yield from 2,6-dibenzyloxy-5-(t-buthyldimethylsiloxy)-3-(p-methoxybenzyloxy)-4,4-dimethyl-8,9-oxiranyl-7-oxononanal 6 by the samarium(II) iodide-mediated intramolecular aldol cyclization.