Endocyclic Double Bond Research Articles

Hygroscopic growth and CCN activity of secondary organic aerosol produced from dark ozonolysis of γ-terpinene

The hygroscopic growth factor (GF) and cloud condensation nuclei (CCN) activity of secondary organic aerosol (SOA) particles produced during dark ozonolysis of γ-terpinene under different reaction conditions were investigated. The SOA particles were produced in the presence or absence of cyclohexane, an OH scavenger; 1,3,5-trimethylbenzene, an anthropogenic volatile organic compound; and (NH4)2SO4 seed particles. A hygroscopicity tandem differential mobility analyzer was used to determine the GFs of the SOA particles at RHs ≤ 93%. For some experiments, a CCN counter was used for size-resolved measurement of CCN activation at supersaturation (S) in the range of 0.1 to 1%. The single hygroscopicity parameter κ was derived from both the GF and CCN measurements. Under subsaturated conditions, all the SOA (except those in the presence of the (NH4)2SO4 seeds) showed small GF values. These GFs demonstrated that SOA mass loading affected the GF. A decrease in the SOA mass loading led to increased GF and corresponding κGFvalues. However, in a supersaturation regime, the SOA mass loading and the size of the particles did not significantly alter the CCN activity of the SOA. Our CCN measurements showed higher κCCN values (κCCN = 0.20–0.24) than those observed in most monoterpene ozonolysis studies (κCCN = 0.1–0.14). This difference may have been due to the presence of the two endocyclic double bonds in the γ-terpinene structure, which may have affected the SOA chemical composition, in contrast to monoterpenes that contain an exocyclic double bond. Our comparisons of sub- and supersaturated conditions showed a larger range of κ values than other experiments. Average κCCN/κGF ratios of ~7 and 14 were obtained in the unseeded SOA experiments at low and high SOA mass loadings, respectively. The average κCCN of 0.23 indicated that the SOA produced during ozonolysis of γ-terpinene exhibited fairly high CCN activity.

Synthesis, characterization and biological activity of Pyrazoline derivatives

Pyrazoline is dihydropyrazole having only one endocyclic double bond. Synthesis of pyrazoline derivatives from chalcones is an active arena of investigation due to established pharmacological result. In present study, chalcones were prepared by reacting of acetophenone with benzaldehyde. Then prepared chalcones react with isoniazid in the presence of glacial acetic acid results pyrazoline derivative. Physical parameters such as color, crystal structure, solubility, melting point, retardation factor (Rf) and % yield was evaluated. Confirmations of structures of all synthesized derivatives, were done by spectroscopic data of IR, 1HNMR and Mass spectroscopy. Also, all synthesized compounds were evaluated for antibacterial activity against B. subtilis, S. aureus, P.aeruginosa and E.coli, and antifungal activity was accomplished against C. albicans and A. niger at the different conc. and concluded that some compounds have excellent antimicrobial activity and most of the synthesized compounds exhibits moderate antimicrobial activity.

Novel Strained Alicyclic Hydrocarbons Based on 5-Methylene-2-norbornene

The paper describes the synthesis of novel strained hydrocarbons based on a\t\t\t\t\tdiene of the norbornene series, namely 5-methylene-2-norbornene, using catalytic\t\t\t\t\tcyclopropanation with diazomethane. The study demonstrated the possibility of\t\t\t\t\tselective cyclopropanation solely along the endocyclic double bond. The\t\t\t\t\tphysicochemical properties of the hydrocarbons were investigated systematically.\t\t\t\t\tThese hydrocarbons were shown to have an advantageous combination of high\t\t\t\t\tdensity, low freezing point, and high energy density value. The study’s findings\t\t\t\t\tindicate that the compounds synthesized are promising as a component of\t\t\t\t\thigh-energy-density fuels for modern jet engines.

Theoretical and Mechanistic Validation of Global Kinetic Parameters of the Inactivation of GABA Aminotransferase by OV329 and CPP-115

((S)-3-Amino-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (OV329) is a recently discovered inactivator of γ-aminobutyric acid aminotransferase (GABA-AT), which has 10 times better inactivation efficiency than its predecessor, CPP-115, despite the only structural difference being an endocyclic double bond in OV329. Both compounds are mechanism-based enzyme inactivators (MBEIs), which inactivate GABA-AT by a similar mechanism. Here, a combination of a variety of computational chemistry tools and experimental methods, including quantum mechanical (QM) calculations, molecular dynamic simulations, progress curve analysis, and deuterium kinetic isotope effect (KIE) experiments, are utilized to comprehensively study the mechanism of inactivation of GABA-AT by CPP-115 and OV329 and account for their experimentally obtained global kinetic parameters kinact and KI. Our first key finding is that the rate-limiting step of the inactivation mechanism is the deprotonation step, and according to QM calculations and the KIE experiments, kinact accurately represents the enhancement of the rate-limiting step for the given mechanism. Second, the present study shows that the widely used simple QM models do not accurately represent the geometric criteria that are present in the enzyme for the deprotonation step. In contrast, QM cluster models successfully represent both the ground state destabilization and the transition state stabilization, as revealed by natural bond orbital analysis. Furthermore, the globally derived KI values for both of the inactivators represent the inhibitor constants for the initial binding complexes (Kd) and indicate the inactivator competition with the substrate according to progress curve analysis and the observed binding isotope effect. The configurational entropy loss accounts for the difference in KI values between the inactivators. The approach we describe in this work can be employed to determine the validity of globally derived parameters in the process of MBEI optimization for given inactivation mechanisms.

Reaction of enamines with semicarbazone-based amidoalkylating reagents: A straightforward synthesis of annulated 1-aminopyrimidin-2-one derivatives

An efficient synthesis of 1-arylideneamino-substituted hexahydro-1H-cyclopenta[d]pyrimidin-2-ones and octahydroquinazolin-2-ones has been developed. The synthesis involves a stereo- and regioselective cascade reaction of the corresponding 4-(tosylmethyl)semicarbazones with 1-morpholinocyclopentene or 1-morpholinocyclohexene to give predominantly bicyclic pyrimidines with an exocyclic CC double bond (80–97%). The later undergo rapid isomerization when heated in THF in the presence of TsOH to form bicyclic pyrimidines with a significant predominance of those with an endocyclic CC double bond (90–97%).

New Insights into Secondary Organic Aerosol Formation: Water Binding to Limonene.

Limonene is an abundant monoterpene in the atmosphere and one of the main precursors of secondary organic aerosol. Understanding its interactions with atmospheric molecules is crucial to explain aerosol formation and the various products obtained from competing reaction pathways. Here, using broadband rotational spectroscopy in combination with computational calculations, we show that limonene effectively interacts with water, forming a variety of complexes. Seven different isomers of limonene-H2O, where water and limonene are connected by O-H···π and C-H···O interactions, have been unambiguously identified. Water has been found to preferentially bind to the endocyclic double bond of limonene. Our findings demonstrate a striking ability of water to attach to limonene and enrich our knowledge on the possible interactions of limonene in the atmosphere.

Comparison of various synthesis methods and synthesis parameters of pyrazoline derivates.

Pyrazoline plays an important role in the development of heterocyclic chemistry theory and is widely used as a synthesis useful in organic synthesis. The structure of the pyrazoline derivative compound contains a 5-membered heterocyclic framework with two nitrogen atoms and one endocyclic double bond. The function of pyrazoline as a fragment was stable enough in the bioactive group to synthesize new compounds with various biological activities. Various methods that could be used for the synthesis of pyrazole derivatives were ultrasonic irradiation, microwave assistance, ionic liquids, grinding techniques, and conventional methods. However, the synthesis of pyrazoline derivatives using conventional methods had many problems, one of which is the product yield, which was <70%. Therefore, this article will discuss the importance of optimizing the synthesis reaction conditions by taking into account several synthesis parameters to get the best organic product results based on conventional methods. A literature search was conducted by employing PubChem, Chemspider Google Scholar, Research Gate, Science Direct, and Elsevier by selecting pyrazoline synthesis based on physicochemical profile, reaction mechanism, and synthesis method.

Synthesis of sp3-Enriched β-Fluoro Sulfonyl Chlorides

AbstractA three-step approach to the synthesis of sp3-enriched β-fluoro sulfonyl chlorides starting from alkenes is reported. The method was successfully applied to a wide range of acyclic and cyclic substrates, bearing either an exocyclic or an endocyclic double bond. The procedure worked with a wide range of substrates and tolerated a number of functional and protecting groups. Moreover, the target cyclic compounds were obtained as single cis diastereomers on a multigram scale. The title compounds are promising building blocks for drug discovery that can be used to obtain sp3-enriched β-fluoro and α,β-unsaturated sulfonamides.

The allylic oxidation of tigliane esters

As part of a study on the structure-activity relationships of the anticancer agent tigilanol tiglate (EBC-46, 2), the allylic oxidation of phorbol triacetate (1c) and of the acetonide of its 3αH-dihydroderivative (5) was investigated. The aim was to introduce an oxygen function at C-5 en route to point-like analogues of 2, but functionalization of C-10 was instead observed. This was followed by oxidative fragmentation of ring B to the 9,10-secotigliane derivative 6 and oxidation of the endocyclic Δ6 double bond to the C-6/C-10 oxygen bridged 7-oxotigliane 7. Despite the over-functionalization of ring B, these observations suggest the possibility to modify positions overlooked in the oxidase phase of tigliane biosynthesis and explore novel areas of the phorbol chemical space.

Key structural features in cis‐carane, (+)‐3‐carene, cis‐pinane, (+)‐α‐pinene, and (−)‐β‐pinene influencing red turpentine beetle primary attraction when released with ethanol

AbstractIn US Pacific Northwest ponderosa pine forests the primary attraction order shown previously for red turpentine beetle, Dendroctonus valens (Coleoptera: Curculionidae: Scolytinae), is (−)‐β‐pinene+ethanol &gt; (+)‐3‐carene+ethanol &gt; (+)‐α‐pinene+ethanol. The monoterpenes are bicyclic C10H16 isomers containing one 6‐carbon ring with one double bond. Both pinenes have a 4‐carbon second ring and differ only by their endocyclic or exocyclic double bond. The (+)‐3‐carene second ring has 3‐carbons; its double bond is endocyclic like (+)‐α‐pinene. Ring system and double bond influences on primary attraction were evaluated by hydrogenating (+)‐3‐carene and (+)‐α‐pinene to cis‐carane and cis‐pinane, respectively. Field test primary attraction strengths were (−)‐β‐pinene+ethanol &gt; cis‐carane+ethanol &gt; cis‐pinane+ethanol &gt; ethanol. In combination with ethanol (i) a double bond is not required in either ring system to attract D. valens, (ii) the cis‐carane bicyclic 3, 6‐carbon ring system provides stronger beetle attraction than the cis‐pinane 4, 6‐carbon bicyclic ring system, and likely structural basis for stronger (+)‐3‐carene attraction over (+)‐α‐pinene, (iii) adding an exocyclic double bond to the 4, 6‐carbon ring system elevates attraction above the 3, 6‐carbon ring system with no double bond, and (iv) the 4, 6‐carbon ring system is a much stronger attractant with an exocyclic rather than endocyclic double bond.

Synthesis of trans-limonene bis-epoxide by stereoselective epoxidation of (R)-(+)-limonene

Naturally occurring terpenes have been identified as key starting materials for bio-based polymers such as non-isocyanate polyurethanes (NIPUs), having a broad range of applications such as thermoset materials, elastomers, or thermoplastics, etc. In this study, synthesis of trans-limonene bis-epoxide (trans-LBE) was carried out via stereoselective di-bromohydration of both the exocyclic and endocyclic double bonds of (R)-(+)-limonene. The effects of various parameters such as reaction temperature, (R)-(+)-limonene:N-bromosuccinimide (NBS) molar ratio and reaction time were investigated. As a result, a 97 % yield of trans-LBE was achieved using 1:2 (R)-(+)-limonene: NBS molar ratio at 60 °C after 5 min of reaction time.

Generation of Leads for γ-Secretase Modulation.

Herein, we disclose three structurally differentiated γ-secretase modulators (GSMs) based on an oxadiazine scaffold. The analogues from series I potently inhibit the generation of Aβ42 in vitro when the substituents at 3 and 4 positions of the oxadiazine moiety adopt an α orientation (cf. 11). To address the concern around potential reactivity of the exocyclic double bond present in series I toward nucleophilic attack, compounds containing either an endocyclic double bond, such as 20 (series II), or devoid of an olefinic moiety, such as 27 (series III), were designed and validated as novel GSMs. Compound 11 and azepine 20 exhibit robust lowering of CSF Aβ42 in rats treated with a 30 mg/kg oral dose.

Polymerization of 5-Ethylidene-2-norbornene in the Presence of Pd–N-Heterocyclic Carbene Complexes with Phosphine and Pyridine Ligands

The polymerization of commercial strained cycloalkene, 5-ethylidene-2-norbornene, in the presence of Pd–N-heterocyclic carbene complexes (two of which are synthesized for the first time) containing phosphine or pyridine ligands is studied. Upon activation with borate Na+[B(3,5-(CF3)2C6H3)4)]–, the studied Pd complexes catalyze the polymerization of 5-ethylidene-2-norbornene according to the addition scheme. Polymerization proceeds selectively and involves only the endocyclic (norbornene) double bond of the monomer, while the exocyclic (ethylidene) double bond remains unaffected. Pd–N-heterocyclic carbene complexes with phosphine ligands are inactive in polymerization, while similar complexes with 3-chloropyridine ligands show a higher activity. Two new Pd complexes are synthesized.

A REVIEW ON PYRAZOLINE DERIVATIVES AS ANTIMICROBIAL AGENT

At present, there is a lot of research about the pyrazoline heterocyclic compound, its ring structure is being changed and new derivatives are being made, many of which have antimicrobial activity over the derivatives. Pyrazoline is the five-member heterocyclic ring which have two N atoms in nearby position and contains two endocyclic double bonds. Noteworthy consideration has been concentrated on pyrazolines and pyrazoline derivative due to their important pharmacological action. Some replaced pyrazolines have been stated near retain particular important pharmacological actions as antimicrobial, antifungal, antineoplastic, antidepressant, insecticidal, anticonvulsant, anti-inflammatory, antibacterial and antitumor properties.

Photoinitiated Thiol-Ene Reactions of Various 2,3-Unsaturated O-, C- S- and N-Glycosides - Scope and Limitations Study.

The photoinitiated thiol−ene addition reaction is a highly stereo‐ and regioselective, and environmentally friendly reaction proceeding under mild conditions, hence it is ideally suited for the synthesis of carbohydrate mimetics. A comprehensive study on UV‐light‐induced reactions of 2,3‐unsaturated O‐, C‐, S‐ and N‐glycosides with various thiols was performed. The effect of experimental parameters and structural variations of the alkenes and thiols on the efficacy and regio‐ and stereoselectivity of the reactions was systematically studied and optimized. The type of anomeric heteroatom was found to profoundly affect the reactivity of 2,3‐unsaturated sugars in the thiol−ene couplings. Hydrothiolation of 2,3‐dideoxy O‐glycosyl enosides efficiently produced the axially C2‐S‐substituted addition products with high to complete regioselectivity. Moderate efficacy and varying regio‐ and stereoselectivity were observed with 2,3‐unsaturated N‐glycosides and no addition occurred onto the endocyclic double bond of C‐glycosides. Upon hydrothiolation of 2,3‐unsaturated S‐glycosides, the addition of thiyl radicals was followed by elimination of the thiyl aglycone resulting in 3‐S‐substituted glycals.

Different Reaction Specificities of F420H2-Dependent Reductases Facilitate Pyrrolobenzodiazepines and Lincomycin To Fit Their Biological Targets.

Antitumor pyrrolobenzodiazepines (PBDs), lincosamide antibiotics, quorum-sensing molecule hormaomycin, and antimicrobial griselimycin are structurally and functionally diverse groups of actinobacterial metabolites. The common feature of these compounds is the incorporation of l-tyrosine- or l-leucine-derived 4-alkyl-l-proline derivatives (APDs) in their structures. Here, we report that the last reaction in the biosynthetic pathway of APDs, catalyzed by F420H2-dependent Apd6 reductases, contributes to the structural diversity of APD precursors. Specifically, the heterologous overproduction of six Apd6 enzymes demonstrated that Apd6 from the biosynthesis of PBDs and hormaomycin can reduce only an endocyclic imine double bond, whereas Apd6 LmbY and partially GriH from the biosyntheses of lincomycin and griselimycin, respectively, also reduce the more inert exocyclic double bond of the same 4-substituted Δ1-pyrroline-2-carboxylic acid substrate, making LmbY and GriH unusual, if not unique, among reductases. Furthermore, the differences in the reaction specificity of the Apd6 reductases determine the formation of the fully saturated APD moiety of lincomycin versus the unsaturated APD moiety of PBDs, providing molecules with optimal shapes to bind their distinct biological targets. Moreover, the Apd6 reductases establish the first F420H2-dependent enzymes from the luciferase-like hydride transferase protein superfamily in the biosynthesis of bioactive molecules. Finally, our bioinformatics analysis demonstrates that Apd6 and their homologues, widely distributed within several bacterial phyla, play a role in the formation of novel yet unknown natural products with incorporated l-proline-like precursors and likely in the microbial central metabolism.

Co(I) complexes with a tetradentate phenanthroline-based PNNP ligand as a potent new metal-ligand cooperation platform.

A series of low spin cobalt(i) complexes bearing a tetradentate phenanthroline-based PNNP ligand (2,9-bis((diphenylphosphanyl)methyl)-1,10-phenanthroline), [CoCl(PNNP)] (1), [CoMe(PNNP)] (2) and [Co(CH2SiMe3)(PNNP)] (3), were synthesized and structurally identified. Complex 3 underwent a structural rearrangement of the PNNP skeleton upon heating to form [Co(PNNP')] (4), which is supported by an asymmetrical PNNP' ligand with a dearomatized phenanthroline backbone. Mechanistic studies supported that the transformation from 3 to 4 was initiated by the homolysis of either a Co-CH2SiMe3 bond or a benzylic C-H bond. Complex 4 achieved H-H bond cleavage of H2 (1 atm) at ambient temperature, to form [Co(PNNP'')] (6), in which two H atoms were incorporated into the endocyclic double bond of the PNNP'' ligand backbone.

Synthesis and Porous Structure of Addition Polymer Based on Dicyclopentadiene

A simple two-stage scheme is proposed for the synthesis of a new porous polymeric material based on dicyclopentadiene, an industrial product and one of the most accessible derivatives of norbornene. The selective addition polymerization of dicyclopentadiene, a bifunctional monomer, proceeds via opening of only one endocyclic double bond and the subsequent hydrogenation of the synthesized product makes it possible to obtain a saturated polymeric material with a high specific surface area (425 m2/g). The porous structure of the hydrogenated addition polydicyclopentadiene is studied in comparison with a similar polymer before hydrogenation using low-temperature nitrogen adsorption/desorption and X-ray powder diffraction. It is shown that the polymeric material obtained has a high thermal stability.

SYNTHESIS AND BIOLOGICAL EVALUATION OF 1-SUBSTITUTED-2-THIENYL- 5-(4-CHLOROPHENYL) PYRAZOLINE DERIVATIVES AS ANTIPROLIFERATIVE AGENTS

Cancer is not a single disease, but a large group of diseases characterized by uncontrolled, rapid and pathological proliferation of abnormally transformed cells. Pyrazoline is a five-membered heterocyclic ring having two adjacent nitrogen atoms within the ring. It has only one endocyclic double bond and is basic in nature. The present study involves synthesis of 1-substituted-2-thienyl-5-(4-chlorophenyl) pyrazoline derivatives. The synthesized compounds were subjected to anticancer screening against SK-OV-3 cells line to determine the growth inhibitory effects of the compounds. Amongst all the derivatives in series (6a-j), the pyrazoline derivatives exhibited potent anticancer activity. All synthesized compounds possessed good to moderate anticancer activity. Compounds 6b and 6c at concentration 80 μg/mL possessed % control growth inhibition comparable to standard drug andriamycin. The order for the % control growth inhibition of SK-OV-3 was found to be 6h&gt; 6j&gt; 6f&gt; 6i&gt; 6e&gt; 6g&gt; 6d&gt; 6a. All the compounds inhibited 50 % of the cell growth at the conc.

Metalated azolo[1,2,4]triazines. II. Generation, C(4)-substituent dependent stability and electrophile trapping of 7-lithiopyrazolo[5,1-c][1,2,4]triazines

7-Lithio-3-tert-butylpyrazolo[5,1-c][1,2,4]triazines have been generated for the first time using one-pot nucleophilic addition and metal-halogen exchange reactions in 7-bromopyrazolo[5,1-c][1,2,4]triazines. It was found that the stability of 7-lithio species depends highly on the substitution pattern at the C(4) ring position. The rate of the pyrazole ring opening reaction roughly followed the order of the electronegativity of substituents: rapid cycle cleavage took place already at −97 °C for C(4) = O, CH–Ar, CH–C≡CPh, while CH–Alk and CH2 substituted derivatives were stable in these conditions (Ar = Ph, 4-tolyl; Alk = t-Bu, n-Bu, n-Pr). Quantum chemical modeling showed that the ring opening is accompanied with simultaneous shift of the Li atom towards N(6). Calculated free activation energies are in range from 12.7 to 15.0 kcal*mol−1. Electrophile trapping of fairly stable 4-alkyl-1,7-metalated derivatives at −97 °C using H2O, DMF or PhCHO allowed the selective side-chain functionalization. Tautomeric exo- and endocyclic double bond equilibrium in the isolated 4-oxo and 4-aryl substituted ring opening products is also discussed on the basis of IR, 1H, 13C NMR, high resolution mass spectra and X-ray powder diffraction analysis.