Cycloalkane Rings Research Articles

Bicyclo[m.n.k]alkane Building Blocks as Promising Benzene and Cycloalkane Isosteres: Multigram Synthesis, Physicochemical and Structural Characterization.

Electrophilic double bond functionalization - intramolecular enolate alkylation sequence was used to obtain a series of bridged and fused bicyclo[m.n.k]alkane derivatives (i. e., bicyclo[4.1.1]octanes, bicyclo[2.2.1]heptanes, bicyclo[3.2.1]octanes, bicyclo[3.1.0]hexanes, and bicyclo[4.2.0]heptanes). The scope and limitations of the method were established, and applicability to the multigram synthesis of target bicyclic compounds was illustrated. Using the developed protocols, over 50 mono- and bifunctional building blocks relevant to medicinal chemistry were prepared. The synthesized compounds are promising isosteres of benzene and cycloalkane rings, which is confirmed by their physicochemical and structural characterization (pKa , LogP, and exit vector parameters (EVP)). "Rules of thumb" for the upcoming isosteric replacement studies were proposed.

Study on quantitative structure of coke deposition in UDH catalyst for acetylene hydrochlorination

ABSTRACT The catalyst made of Au, Cu and K according to a certain ratio which is defined as a UDH catalyst has a great catalytic effect on acetylene hydrochlorination. In order to clarify the formation mechanism of coke deposition in catalyst, the structure of coke deposition was quantified. Carbon deposits in the UDH catalyst are separated using Soxhlet extraction and rotary evaporation. Experimental techniques like gel chromatography, elemental analysis, H-NMR and FT-IR were applied for the characterization of coke deposition. The quantitative structure of the coke deposition was evaluated by the improved B-L method. The results show that the average molecular formula of the coke deposition is C40.82H33Cl15.55 which is a complex multiple-ring structure containing seven aromatic rings and five six-membered cycloalkane rings. The aromatic carbon fraction of the calculated coke deposition is 0.623, and the ratio of hydrogen to carbon atomic which are not replaced in aromatic ring moieties is 0.313. These results indicate that in the side reaction of acetylene hydrochlorination, substances with the ring structure are more likely to be generated, and the ring structure continues to increase, eventually forming coke deposition.

Molecular Characteristics of Jimusaer Shale Oil from Xinjiang, China.

Increasing attention is currently obtained by the exploitation and utilization of unconventional energy sources globally. Jimusaer shale oil (JSO) was prepared by dry distillation from oil shale in Jimusaer, Xinjiang, China. Using n-heptane and toluene as solvents, saturate (SA), aromatic (AR), resin (RE), and asphaltene (AS) samples were produced from JSO. Samples were subsequently analyzed by elemental analysis (EA), thermogravimetric analysis (TG-DTG), infrared analysis (FT-IR), high-performance gel chromatography (GPC), and nuclear magnetic resonance (1H-NMR and 13C-NMR). In terms of basic properties, element content, classification of combustible minerals, and refining performance, JSO, which has a high H/C value, low carbon residue yield, low metal content, and excellent refining-processing performance, is considered a high-quality shale oil compared with the shale oil produced in other areas. The refining performance of JSO is even comparable with petroleum. According to column chromatography, the contents of SA, AR, RE, and AS in JSO are 54.32, 18.86, 25.81, and 1.01%, respectively. The results of FT-IR and NMR (1H-NMR and 13C-NMR) demonstrated that the chain alkane or aromatic cycloalkyl substituents of SA, AR, and RE decrease sequentially, while the number of aromatic rings and cycloalkane rings and the degree of condensation increase sequentially. These results indicate that the chain alkanes with a small number of cycloalkanes are the main component of SA. The AR and RE contain more thick-ring aromatic hydrocarbons. According to GPC, the molecular weight (Mn) of JSO is 845 g·mol–1, and those of SA, AR, and RE are 702, 1107, and 2218 g·mol–1, respectively. The estimated molecular formulas (Maf) of JSO, SA, AR, and RE, which were calculated based on the combined results of GPC and EA, are C57.91H115.60O1.38N0.79S0.04, C48.02H101.79O0.69N0.85S0.03, C76.96H137.16O1.08N1.87S0.09, and C156.24H247.75O1.46N4.42S0.32.

Self-assembly and phase transition properties of pure archaeal tetraether lipids

Lipid membrane compartments are universal features of life, but different organisms evolved diverse lipids to meet specific physiological and ecological requirements. Glycerol dibiphytanyl glycerol tetraethers (GDGT) are some of the most unusual membrane lipids identified in nature. GDGT lipids are characterized by multiple branching, ether linkages, cycloalkane rings, and often span the entire length of the membranes. These lipids are the primary constituents of the cell membranes of many Archaea, some of which are extremophilic organisms.

Ligand-redox assisted nickel catalysis toward stereoselective synthesis of (n+1)-membered cycloalkanes from 1,n-diols with methyl ketones.

A well-defined, bench-stable nickel catalyst is presented here, that can facilitate double alkylation of a methyl ketone to realize a wide variety of cycloalkanes. The performance of the catalyst depends on the ligand redox process comprising an azo-hydrazo couple. The source of the bis electrophile in this double alkylation is a 1,n-diol, so that (n+1)-membered cycloalkanes can be furnished in a stereoselective manner. The reaction follows a cascade of dehydrogenation/hydrogenation reactions and adopts a borrowing hydrogen (BH) method. A thorough mechanistic analysis including the interception of key radical intermediates and DFT calculations supports the ligand radical-mediated dehydrogenation and hydrogenation reactions, which is quite rare in BH chemistry. In particular, this radical-promoted hydrogenation is distinctly different from conventional hydrogenations involving a metal hydride and complementary to the ubiquitous two-electron driven dehydrogenation/hydrogenation reactions.

Steroidal molecules as swiftly acting therapeutics

The A steroid is a sort of natural exacerbate that contains a features plan of four cycloalkane rings that are joined to one another. Steroid biosynthesis is an anabolic metabolic pathway that produces steroids from basic forerunners. Steroid, any of a class of regular or engineered natural mixes portrayed by a sub-atomic structure of 17 carbon particles orchestrated in four rings. Steroids are significant in science, science, and medication

Structural Investigation, UV–Vis Analysis and Crystal Packing of Spiro[chromeno[4,3-b]quinoline-6,1′-cycloalkan]-7-amine: Novel Tacrine Hybrids by Single Crystal X-Ray Diffraction

The structure of four spiro[chromeno[4,3-b]quinoline-6,1′-cycloalkan]-7-amine (1–4) was determined by X-ray diffraction methods. The quinoline rings were obtained as almost planar structures, with an RMS deviation within a range of 0.0345–0.0641 A, while the chromene rings are not planar. Moreover, the cycloalkane rings are attached to the chromene in spiro form. Three of the four compounds crystallize as solvates—one with ethanol and the other two with water. The crystal packing for compounds 1–4 is discussed in terms of intermolecular interactions, and it is shown that the crystal packing of these heterocycles is governed by: strong O–H···N and N–H···O hydrogen bonds; weak C–H···O and C–H···N hydrogen bonds; and very weak C–H···Cl, C–H···Br, and C–H···π interactions. Also, π···π and lone pair···π interactions are present in the crystal packing of the heterocycles. These interactions lead to the formation of endless chains along a plane, as well as supramolecular dimers and the arrangement of molecules in layers. Additionally, UV–Vis absorption spectra properties are also discussed. The structure of four spiro[chromeno[4,3-b]quinoline-6,1’-cycloalkan]-7-amines are determined by single crystal X-ray diffraction. The crystal packing is discussed in terms of intermolecular interactions (strong O–H···N and N–H···O hydrogen bonds; weak C–H···O and C–H···N hydrogen bonds; and very weak C–H···Cl, C–H···Br, and C–H···π interactions). Also, π···π and lone pair π interactions are present in the crystal packing of the heterocycles.

Biotechnological transformation of hydrocortisone to 16α-hydroxy hydrocortisone by Streptomyces roseochromogenes

Streptomyces roseochromogenes is able to hydroxylate steroid compounds in different positions of their cycloalkane rings thanks to a cytochrome P-450 multi-enzyme complex. In this paper, the hydroxylation of the hydrocortisone in the 16α position, performed by bacterial whole cells, was investigated in both shake flask and fermentation conditions; the best settings for both cellular growth and transformation reaction were studied by investigating the optimal medium composition, the kinetic of conversion, the most suitable substrate concentration and the preferred addition timing. Using newly formulated malt extract- and yeast extract-based media, a 16α-hydrohydrocortisone concentration of 0.2 ± 0.01 g L(-1) was reached in shake flasks. Batch experiments in a 2-L fermentor established the reproducibility and robustness of the biotransformation, while a pulsed batch fermentation strategy allowed the production to increase up to 0.508 ± 0.01 g L(-1). By-product formation was investigated, and two new derivates of the hydrocortisone obtained during the bacterial transformation reaction and unknown so far, a C-20 hydroxy derivate and a C-21 N-acetamide one, were determined by NMR analyses.

Do 12-Membered Cycloalkane Rings Only Exist As One Conformation in the Solid-State? A Detailed Solid-State Analysis Involving Polymorphs ofN,N′-Biscyclododecyl Pyromellitic Diimide

Conformational flexibility in molecules plays a key role in many chemical and biological processes. It is a common belief that the larger the cycloalkane the more flexible it will be, and the more ...

Catalytic activity of halohydrin dehalogenases towards spiroepoxides

A novel activity of halohydrin dehalogenases towards spiroepoxides has been found. The enzyme from Arthrobacter sp. (HheA) catalysed highly regioselective azidolysis of spiroepoxides containing 5, 6 and 7-membered cycloalkane rings, while the enzyme from Agrobacterium radiobacter (HheC), besides high regioselectivity, also displayed moderate to high enantioselectivity (E up to >200) that can be applied for the kinetic resolution of chiral spiroepoxides. The orientations of spiroepoxides in the active site of halohydrin dehalogenases were studied by quantum-chemical calculations and docking simulations. Analyses of the complexes obtained revealed the origins of diastereoselectivity and enantioselectivity of the investigated biotransformations.

N]Imperilenes: Stacked [n]Trannulenes Separated by Planar Cycloalkane Rings

Two trannulene moieties fused to each other by means of perfectly planar cycloalkane rings comprise an interesting class of molecules (above) named "imperilenes". Based on computed geometries and NICS(zz) values, only the [5], [7], and [9]imperilene singlet states as well as the 4+ charged [4], [6], and [8]imperilenes and their higher energy neutral quintet states are aromatic. The π electron systems of the individual trannulene rings, rather than the overall electron count, determine the behavior.

Synthesis of structurally constrained 4-quinazolinone derivatives with a tetrahedral C-2 atom present in three rings

The reaction of 2-aminobenzamides with 2-oxocyclopentane-, 2-oxocyclohexane-, and 2-oxocycloheptaneacetic acids esters was found to give 7a,8,9,10-tetrahydrocyclopenta[2,3]pyrrolo[1,2- a]quinazoline-6,12(7 H,11 H)-diones, 7,7a,8,9,10,11-hexahydro-6 H-indolo[1,7 a- a]quinazoline-6,13(12 H)-diones, and 7a,8,9,10,11,12-hexahydrocyclohepta[2,3]pyrrolo[1,2- a]quinazoline-6,14(7 H,13 H)-diones, respectively. The relative configuration with the cis-fused butyrolactam and cycloalkane rings was assigned to the prepared compounds on the basis of an X-ray crystallographic study.

Structure, conformation and hydrogen bonding of two amino-cycloalkanespiro-5-hydantoins

AbstractThe crystal structures of 3-amino-cycloheptanespiro-4′-imidazolidine-2′,5′-dione (I) {systematic name: 3-amino-1,3-diazaspiro[4.6] undecane-2,4-dione} and 3-amino-cyclooctanespiro-4′-imidazolidine-2′,5′-dione (II) {systematic name: 3-amino-1,3-diazaspiro[4.7] dodecane-2,4-dione}, have been determined. In both compounds the polar hydantoin groups cause molecules to aggregate via N-H...O and N-H...N interactions, forming a layer structure, in which the cycloalkane rings project outwards from the central, more polar, region. The observed molecular structure is compared with that calculated by density functional theory methods.

Crystal structures and physical properties of donor type dithiolene complexes with cycloalkane rings

Metal bis-dithiolene complexes have been intensively studied as conducting materials. Among them, acceptor type complexes provide various anion radical salts which exhibit superconducting and metallic behavior. [1] On the other hand, neither a metal nor a superconductor has been obtained from donor type complexes except for a salt of [Ni(dddt)2]. [2] In this work, we examined modification of the dddt complex with terminal cycloalkane rings, and developed [Ni(Cn-dddt)2] (n = 3, 4, 5, 6) to expand the materials chemistry of the donor type complexes. In the crystals of the neutral complexes, the cycloalkane rings exhibited various conformations which would affect physical properties in their cation radical salts. We succeeded in electrochemical crystallization of new cation radical salt [Ni(C3-dddt)2]3(BF4)2. Other salts were also obtained by similar procedures. We will discuss their electrical property of the salts based on the crystal structure.

Hydrogen bonding patterns in a series of 1-arylcycloalkanecarboxamides

Single-crystal structures of five 1-arylcycloalkanecarboxamides, viz.1-phenylcyclopentanecarboxamide (1), 1-phenylcyclohexanecarboxamide (2), 1-(2-fluorophenyl)cyclohexanecarboxamide (3), 1-(2-chlorophenyl)cyclohexanecarboxamide (4) and 1-(2-bromophenyl)-cyclohexanecarboxamide (5), are reported. The primary hydrogen-bonded motif consists of centrosymmetric or non-centrosymmetric R22(8) dimers between the carboxamide functional groups. In compound 1, the dimers are further linked by hydrogen bonds to form infinite two-dimensional sheets, while in 4 and 5 additional hydrogen bonding with molecules not involved in dimer formation links the dimers into infinite chains. The cycloalkane rings in the five compounds adopt noticeably different conformations. As a consequence of these various effects, none of the five compounds is isostructural.

Structure-activity relationships of antineoplastic ring-substituted ether phospholipid derivatives

Previous studies have shown that alkylphosphocholines (APCs) exhibit strong antineoplastic activity against various tumour cell lines in vitro and in several animal models. The current study was designed to investigate the influence of cycloalkane rings on the antiproliferative activity of APCs against a panel of eight human and animal cell lines (PC3, MCF7, A431, Hela, PC12, U937, K562, CHO). Specifically, we explored the effect of the presence of 4-alkylidenecyclohexyl and cycloalkylidene groups in alkoxyethyl and alkoxyphosphodiester ether lipids, respectively. In addition, the haemolytic activity of the new ring-substituted ether phospholipids (EP) was evaluated. Cells were exposed to various concentrations of the compounds for 72 h. The cytotoxicity was determined with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] dye reduction assay. Similarly, red blood cells were distributed in 96-well microplates and treated with the test compounds at concentrations ranging from 100 to 6.25 microM for 1 h. After centrifugation, the absorbance of the supernatants was measured at 550 nm. The majority of the compounds tested exhibited significant cytotoxic activity which depended on both the ring size and position with respect to the phosphate moiety, as well as the head group. Among the cycloalkylidene series the 11-adamantylideneundecyl-substituted N-methylmorpholino EP 13 was the most potent and exhibited broad-spectrum anticancer activity comparable to or superior to that of hexadecylphosphocholine (HePC). All the adamantylidene-substituted EPs were nonhaemolytic (concentration that exhibits 50% haemolytic activity, HC(50), >100 microM). Furthermore, the cyclohexylidene-substituted analogues were more potent against the cell lines tested, with the exception of U937 and K562, than the cyclodecapentylidene-substituted compounds. Hydrogenation of the double bond in the cycloalkylidene-substituted EPs (compounds 14 and 15) resulted in improvement of anticancer activity. Among the 2-(4-alkylidenecyclohexyloxy)ethyl EPs, 2-(4-hexadylidenecyclohexyloxy)ethyl phosphocholine (22) possessed the highest broad-spectrum cytotoxic activity than all the other analogues of this series and was nonhaemolytic (HC(50) >100 microM). In general, the 2-(4-alkylidenecyclohexyloxy)ethyl-substituted EPs were more active against the more resistant cell lines U937, K562 and CHO than HePC. The presence of cycloalkane rings in the lipid portion of APCs reduces haemolytic effects compared to HePC and in several analogues results in improved antineoplastic activity.

Sequential Birch Reduction—Allylation and Cope Rearrangement of o‐Anisic Acid Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Sequential Birch reduction–allylation and Cope rearrangement of o-anisic acid derivatives

A new method for the construction of quaternary centers on cycloalkane rings is reported. The Cope rearrangement of 4-methyl-2-allyl-2-( N-pyrrolidinyl)-carboxamide-3-cyclohexenone yields 4-methyl-4-allyl-2-( N-pyrrolidinyl)-carboxamide-2-cyclohexenone in high yield. The rearrangement substrates are easily generated from Birch reduction–allylation of o-anisic acid derivatives.

Peptide helices with pendant cycloalkane rings. Characterization of conformations of 1-aminocyclooctane-1-carboxylic acid (Ac8c) residues in peptides.

A pentapeptide, Boc-Leu-Ac8c-Ala-Leu-Ac8c-OMe 1, an octapeptide, Boc-Leu-Ac8c-Ala-Leu-Ac8c-Ala-Leu-Ac8c-OMe 2 and a tripeptide, Boc-Aib-Ac8c-Aib-OMe 3 containing the 1-aminocyclooctane-1-carboxylic acid residue (Ac8c) were synthesized and conformationally characterized by x-ray diffraction studies in the crystal state. Peptides 1 and 2 were also studied by NMR in CDC13 solution. Peptide 1 adopts a purely 3(10)-helical conformation in crystals, stabilized by three intramolecular 1 <-- 4 hydrogen bonds. Peptide 2 in crystals is largely 3(10)-helical with distortion in the backbone at the N-terminus by the insertion of a water molecule between Ac8c (2) CO and Ala (6) NH groups. Peptide 3 forms a C10-ring structure, i.e. a type III (III') beta- turn conformation stabilized by an intramolecular 1 <-- 4 hydrogen bond. Five cyclooctane rings assume boat-chair conformations, whereas the sixth [Ac8c(8) in 2] is appreciably distorted, resembling a chiral intermediate in the pseudorotational pathway from the boat-chair to the twisted boat-chair conformation. Internal bond angles of the cyclooctane rings are appreciably distorted from the tetrahedral value, a characteristic feature of the cyclooctane ring. Peptide 1 crystallized in the space group P212121 with a = 11.900(4) A, b = 18.728(6) A, c = 20.471(3) A and Z = 4. The final R1 and wR2 values are 0.0753 and 0.2107, respectively, for 3901 observed reflections [Fo > or = 3 sigma (Fo)]. Peptide 2 crystallized in space group P21 with a = 12.961(5) A, b = 17.710(10) A, c = 15.101(7) A, beta = 108.45(4) degrees and Z = 2. The final R1 and wR2 values are 0.0906 and 0.1832, respectively, for 2743 observed reflections [Fo > or = 3sigma (Fo)]. 1H-NMR studies on both the peptides strongly suggest the persistence of 3(10)-helical conformations in solution. Peptide 3 crystallized in the space group P21/n, with a = 10.018(1) A, b = 20.725(1) A, c = 12.915(1) A and Z = 4. The final R1 and wR2 values are 0.0411 and 0.1105, respectively, for 3634 observed reflections [Fo > or = 4sigma (Fo)].

On triazoles XLVII. Synthesis of 1,3a,5,6,ωc‐pentaazacycloalka[e]acenaphthylenes

AbstractTo study the influence of planar or bulky cycloalkane rings attached to the 1,3a,5,6,ωc‐pentaazaacen‐aphthylenes to the reactivity of their 4‐alkylthio group toward amines ‐ an unexpected reaction observed recently at 1,3a,5,6,10c‐pentaazaacephenanthrylenes (5b, n = 4) ‐ different size 1,3a,5,6,ωc‐pentaazacyclo‐alka[e]acenaphthylenes (5a, n = 3; 5c, n = 5; 5d, n = 6; or 5e, n = 10) were synthesised and their spectral data compared with that of 5b (n = 4). Based on the analogy of the chemical shifts of carbon atoms at position 4 with that of 5b, similar electronic structure and thus a possibility of an analogous nucleophilic attack of amines was proposed and subsequently proved by a preparative method.