Ketone Moiety Research Articles

Correction to: Synthesis and characterization of processable aromatic poly(ether ether ketone amide)s modified by phenoxy and 1,3 ketone moiety linkages

Correction to: Synthesis and characterization of processable aromatic poly(ether ether ketone amide)s modified by phenoxy and 1,3 ketone moiety linkages

Synthesis and characterization of processable aromatic poly(ether ether ketone amide)s modified by phenoxy and 1,3 ketone moiety linkages

New series of aromatic poly(ether ether ketone amide)s were synthesized by low-temperature solution polymerization of novel aromatic diamine, namely 1,3-bis-4′-(4″-aminophenoxy benzoyl)benzene (XIV), and aromatic diacid chlorides, viz. isophthaloyl chloride (IPC) and terephthaloyl chloride (TPC). Co-poly(ether ether ketone amide)s were also synthesized by employing various mole proportions of IPC and TPC with diamine (XIV). These poly(ether ether ketone amide)s were characterized by FTIR, solubility, inherent viscosity, TGA, DSC, and XRD. Inherent viscosities of these poly(ether ether ketone amide)s were in the range of 0.41–0.52 dL/g in DMAc, indicating the formation of moderate to high molecular weight of polymers. Poly(ether ether ketone amide)s showed good solubility in polar aprotic solvents such as N,N-dimethyl acetamide (DMAc), N-methyl 2-pyrrolidone, N,N-dimethylformamide, and dimethyl sulfoxide. These poly(ether ether ketone amide)s had glass transition temperatures, as determined by DSC, in the range of 252–302 °C. These polymers showed similar decomposition patterns and had no weight loss below 335 °C, and temperatures for 10% weight loss (T10) were in the range of 397–406 °C, indicating that these polymers showed good thermal stability.

How does cross-conjugation influence thiol additions to enones? A computational study of thiol trapping by the naturally occurring divinyl ketones zerumbone and α-santonin.

Density functional theory calculations are reported which explore how the kinetics and thermodynamics of thiol additions to enones are affected by the incorporation of the enone into a cross-conjugated divinyl ketone moiety. Computations with ωB97X-D//M06-2X indicate that in the parent acyclic system (1,4-pentadien-3-one), cross-conjugation has a small stabilizing effect on the thiol adduct, making the ΔG for the addition slightly more negative, and a larger stabilizing effect on the transition state, lowering ΔG‡. By contrast, in the parent six-membered cyclic system (2,5-cyclohexadien-1-one), cross-conjugation makes ΔG significantly less negative while causing only a small increase in ΔG‡. Both scenarios correspond to a more reversible addition. Thiol additions to two naturally occurring divinyl ketones, zerumbone and α-santonin, are examined. Previous NMR-based assays had shown that zerumbone forms mono- and bis-thiol adducts while α-santonin showed no detectable adduct formation. Computations reveal that the eleven-membered ring structure of zerumbone accelerates thiol trapping, relative to an analogous acyclic model. For α-santonin, the computations reveal that thiol addition is actually also rather facile, and it likely does occur, but the adduct is unstable and rapidly eliminates the thiol. These results illustrate that the inability to detect a thiol adduct in an experimental assay does not necessarily imply that the adduct does not form; instead it may simply be a manifestation of a rapid addition/elimination equilibrium in which the adduct concentration is below the limits of detectability.

Catalytic Stereoselective Borylative Transannular Reactions

AbstractMedium‐sized carbocycles containing an α,β‐unsaturated ketone moiety as Michael acceptor site and a ketone moiety as internal electrophilic site are ideal substrates to conduct Cu(I)‐catalyzed conjugated borylation followed by electrophilic intramolecular trapping that results into a pioneer transannular borylative ring closing reaction. The relative configuration of three adjacent stereocenters is controlled, giving access to a single diastereoisomer for a wide range of substrates tested. Moreover, when a chiral ligand is incorporated, the reaction provides enantioenriched polycyclic products with up to 99 % ee.

Catalytic Stereoselective Borylative Transannular Reactions.

Medium-sized carbocycles containing an α,β-unsaturated ketone moiety as Michael acceptor site and a ketone moiety as internal electrophilic site are ideal substrates to conduct Cu(I)-catalyzed conjugated borylation followed by electrophilic intramolecular trapping that results into a pioneer transannular borylative ring closing reaction. The relative configuration of three adjacent stereocenters is controlled, giving access to a single diastereoisomer for a wide range of substrates tested. Moreover, when a chiral ligand is incorporated, the reaction provides enantioenriched polycyclic products with up to 99 % ee.

Isolation of new streptimidone derivatives, glutarimide antibiotics from Streptomyces sp. W3002 using LC-MS-guided screening.

A LC-MS-guided screening led to the isolation of two new streptimidone derivatives (2 and 3) containing a glutarimide ring and two glutarimide ring-opened compounds (4 and 5) along with a known glutarimide-containing polyketide, streptimidone (1) from Streptomyces sp. W3002 strain. Their structures were elucidated by MS and NMR spectroscopic analyses and by comparison with data from the literature. Compound 2 is a non-hydroxylated analog at the C-5 position of streptimidone. The structure of 3 was determined as a streptimidone derivative possessing the α, β-unsaturated ketone moiety at positions C-5 and C-6. Compound 4 had similar chemical shifts and splitting patterns with 3, but the glutarimide ring is opened. Compound 5 closely resembles that of 4 with the only difference being the existence of an additional methoxy group instead of an amide group. Streptimidone (1) and 3 showed weak cytotoxic activity against three human cancer cell lines, respectively.

Chemoselective Hydrosilylation of Olefin/Ketone Catalyzed by Iminobipyridine Fe and Co complexes

AbstractThe chemoselective hydrosilylation of olefins and ketones catalyzed by Fe and Co complexes bearing an iminobipyridine derivative ligand was investigated. The reaction of a 1 : 1 mixture of styrene and acetophenone over the Fe catalyst achieved selective hydrosilylation of acetophenone. In contrast, the corresponding Co complex showed the opposite selectivity‐styrene‐selective hydrosilylation. The reaction of 3‐acetylstyrene with both olefin and ketone moieties in the molecule showed that the Co complex catalyzed olefin‐selective hydrosilylation. In contrast, the addition of pyridine to the Co‐catalyzed system showed the opposite chemoselectivity, affording the ketone hydrosilylated product. The chemoselectivity of olefin/ketone hydrosilylation was switched by replacing the central metal of the complex with the iminobipyridine derivative ligand and by changing the simple reaction conditions (absence or presence of pyridine) using an identical Co complex.

Investigation of Reactions Between Isothiazolinones and Cysteamine by Reactive Paper Spray Ionization Mass Spectrometry (Reactive PSI MS)

Reactive ionization with atmospheric pressure ionization (API) methods have been utilized for mass spectrometry (MS) to enhance ionization efficiency of an analyte, to recognize a specific functional group of an analyte, and to investigate reaction pathways or intermediates for a certain in situ reaction. Paper spray ionization (PSI) is one of the major API techniques for reactive ionization. In reactive PSI, one of the reactants is usually spotted onto a paper tip and the other reactant is delivered through a spraying solution. After in situ reaction, reaction products are transported to the end of the tip and ionized. In this study, we investigated reactions between isothiazolinones (ITs) and cysteamine (CA) by reactive PSI MS. An IT is a heterocyclic compound that has a conjugated ketone moiety and used as a biocide or a preservative. CA is a stable aminothiol that is often used as a bifunctional covalent modifier. Through reactive PSI MS of ITs with CA, we found that a covalent modification of an IT by CA was possible and sensitivities for ITs were improved compared to conventional PSI MS of ITs that did not employ CA. In addition, possible reaction pathways between ITs and CA during reactive PSI were suggested although we could not confirm a specific reaction pathway in the current study.

Fibrane the reduced derivative of fenofibrate

Synthetic routes for the preparation of (i) isopropyl 2-(4-(4-chlorobenzyl)phenoxy)-2-methyl propanoate (Reduced Fenofibrate, Fibrane) (2) from isopropyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate (Fenofibrate) (1) in a single step is established in good yield and purity under mild conditions. The newly synthesized derivative of Fenofibrate has been characterized by NMR and IR spectroscopy techniques. Selective conversion of biphenyl ketone moiety, in the presence of ester carbonyl group in Fenofibrate to its corresponding alkane can be performed by Pd catalyst reduction with hydrogen transfer agent ammonium formate.

Piperine Is a Mechanism-Based Inactivator of CYP3A.

Piperine (PPR) is the representative alkaloid component of the piper species (family: Piperaceae). Our rapid screening study found PPR caused time-dependent inhibition of cytochrome P450s (CYP) 3A and 2D6, and CYP3A was inactivated the most. Further study demonstrated that PPR is a time-, concentration-, and NADPH-dependent inhibitor of CYP3A, and significant loss (49.5% ± 3.9%) of CYP3A activity was observed after 20minute incubations with 80 μM PPR at 37°C. The values of K I and k inact were 30.7 μM and 0.041 minutes-1, respectively. CYP3A competitive inhibitor ketoconazole showed protective effect against the enzyme inactivation. Superoxide dismutase/catalase and GSH displayed minor protection against the PPR-caused enzyme inactivation. Ferricyanide partially reduced the enzyme inhibition by PPR. Additionally, NADPH-dependent formation of reactive metabolites from PPR were found in human liver microsomal incubation mixtures. An ortho-quinone intermediate was trapped by NAC in microsomal incubations with PPR. DM-PPR, demethylene metabolite of PPR, showed weak enzyme inactivation relative to that caused by PPR. It appears that both carbene and ortho-quinone intermediates were involved in the inactivation of CYP3A caused by PPR. SIGNIFICANCE STATEMENT: CYP3A subfamily members (mainly CYP3A4 and CYP3A5) play a critical role in drug metabolism. Piperine (PPR), a methylenedioxyphenyl derivative combined with an unsaturated ketone, is the major active ingredient of pepper. PPR revealed time-, concentration-, and NADPH-dependent inhibitory effect on CYP3A. Carbene and quinone metabolites were both involved in the observed CYP3A inactivation by PPR. Apparently, the unsaturated ketone moiety did not participate in the enzyme inactivation. The present study sounds an alert of potential risk for food-drug interactions.

Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds.

BackgroundNeolaxiflorin B is derived from ent-kaurane like laxiflorin J and eriocalyxin B with a relatively low potency as an antitumor agent. During preliminary structure–activity relationship studies, the α,β-unsaturated ketone (enone) system is an important active group.MethodsSeven neolaxiflorin B derivatives containing α,β-unsaturated ketone moieties were synthesized. In vitro, activity was evaluated against three human tumor cell lines and a rat myogenic cell line (HepG2, NSCLC-H292, SNU-1040, and L6, respectively) by MTT assay.ResultsCompound 15 appeared a promising antitumor lead due to its cytotoxic potency and relatively high selectivity, with an SI value of 13.14. Flow cytometry analysis was conducted to show that NSCLC-H292 cells were blocked in the G0/G1 phase in the presence of compound 15, thus inhibiting the proliferation of tumor cells.ConclusionThis study has revealed that compound 15 is a promising antitumor lead due to the cytotoxic potencies and the high selectivity it displayed when compared to natural counterparts.

Antithrombotic and Antiplatelet Activities of New Isohopane Triterpene From the Roots of Rubia akane

A new isohopane triterpenoid (1) and two known triterpenoids (2-3) were isolated from the roots of Rubia akane (Rubiaceae). The molecular formula C30H46O4 of 1 was determined by HRESIMS. Detailed NMR spectroscopic data analysis suggested that compound 1 is a new isohopane triterpenoid with a ketone moiety at C-16. Based on the key NOE correlations of H-3/H-5 and H-21/H3-28, compound 1 was determined as 3β-hydroxy-16-oxo-21β-isohop-22(29)-en-24-oic acid. The anticoagulant activities of new isohopane 1 were evaluated by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin (Factor IIa, FIIa) and activated factor X (FXa). The effects of 1 on expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated in tumor necrosis factor-α activated human umbilical vein endothelial cells. Treatment with 1 (200 μM) resulted in the prolongation of aPTT and PT and the inhibition of relative thrombin (28%) and FXa (29%) activities. In addition, 1 inhibited thrombin-catalyzed fibrin polymerization (18% inhibition at 100 μM) and platelet aggregation (21.8% inhibition at 100 μM). Compound 1 also elicited anticoagulant effects in mice in a dose-dependent manner ranging from 18.8 to 94.0 μg/mouse. In addition, treatment with 1 resulted in significant reduction of the PAI-1 to t-PA ratio (25% decreased). Collectively, the new isohopane triterpenoid 1 possesses antithrombotic activities and offers a basis for the development of a new anticoagulant agent.

Inhibition of melanin production by sesquiterpene lactones from Saussurea lappa and their analogues

This research is aimed towards the discovery of a novel skin whitening agent from sesquiterpene lactones. We screened nine sesquiterpene lactones from Saussurea lappa root extracts, costunolide (1), α-, β-, γ-cyclocostunolides (2, 3, 4), santamarine (5), reynosin (6), arbuscirin A (7), dehydrocostus lactone (8), and 11β, 13-dehydrocostus lactone (9), for their melanin inhibitory activity in B16 melanoma cells. This study was focused on the inhibition of the extracellular melanin content. The screening results revealed that only α-cyclocostunolide (2) showed notable inhibition of the melanin production, particularly the extracellular melanin content, with an IC50 value of 5.75 μM. In addition, structure-activity relationship (SAR) of 12 sesquiterpene lactone analogues with reference to their melanin inhibitory activity was also investigated. However, none of the analogues were found to show any significant melanin inhibitory activity. To the best of our knowledge the above study is the first SAR investigation involving the melanin inhibitory activity of sesquiterpene lactones. It established that eudesmanolide-type lactone having a double bond between C3 and C4 showed the most efficient melanin inhibition. Additionally, the presence of a hydroxyl, ketone or ester moiety as the C1-substituent markedly decreased the melanin inhibitory activity. Thus, these findings suggest that α-cyclocostunolide (2) might be useful in the therapy of skin disorders.

Synthesis of Functionalized Organoboron/Silicon Compounds by Copper-Catalyzed Coupling of Alkylsilyl Peroxides and Diboron/Silylborane Reagents

The facile synthesis of functionalized organoboron/silicon compounds by copper-catalyzed coupling of alkylsilyl peroxides and diboron/silylborane reagents is reported. The reactions proceed smoothly under mild, neutral conditions in short reaction times to generate organoboron/silicon compounds bearing a ketone moiety, which are useful synthetic intermediates that are otherwise difficult to access. The results of mechanistic investigations suggest the radical-mediated formation of carbon-boron and carbon-silicon bonds via β-scission of alkoxy radicals.

Anticancer activity of the thiosemicarbazones that are based on di-2-pyridine ketone and quinoline moiety

Thiosemicarbazones (TSC) are a subclass of iron-chelating agents that are believed to have an anticancer activity. The high potential for the application of this compound class can be illustrated by a fact that three TSC have entered clinical trials. The ability to chelate metal ions results in several biochemical changes in the cellular metabolism and growth. An important factor that determines the antitumor activity of TSC is a level of iron regulatory proteins and the antioxidant potential that is specific for each type of cancer cell. However, despite the increasing interest in TSC, their mechanism of anticancer activity is still unclear. For a more effective and rational design, it is crucial to determine and describe the abovementioned issues. In this report, we describe a series of new TSC that are designed on the four main structural scaffolds. The anticancer activity of these compounds was evaluated against a panel of cancer cell lines including colon and breast cancers and gliomas. Special attention was paid to the metal-dependent proteins. The impact of the tested TSC on the cell cycle and redox homeostasis was also determined. These results confirm a p53-independent mechanism of apoptosis.

One-Electron Reduction of 2-Mono(2,6-diisopropylphenylimino)acenaphthene-1-one (dpp-mian).

The electrochemical characteristics of 2-mono(2,6-diisopropylphenylimino)acenaphthene-1-one (dpp-mian) have been investigated. One-electron reduction of dpp-mian involves the iminoketone fragment, which is revealed by the EPR spectrum obtained after the electrolysis of the dpp-mian solution in tetrahydrofuran (THF). The reduction of dpp-mian with one equivalent of metallic potassium leads to a similar EPR spectrum. The sodium complex [(dpp-mian)Na(dme)]2 (1) produces an EPR signal with hyperfine coupling on the nitrogen atom of the iminoketone fragment of the dpp-mian ligand. Dpp-mian can also be reduced in a one-electron process by SnCl2 ×(dioxane). In this case, complex (dpp-mian)2 SnCl2 (2) is formed, with the tin atom displaying an oxidation state of +4. Tin(II) chloride dihydrate, SnCl2 ×2(H2 O), also reduces dpp-mian, but the two ligands bound to tin in the product form a new carbon-carbon bond between the ketone moieties of the dpp-mian monoanions to form complex (bis-dpp-mian)HSnCl3 (3). Metallic tin reduces dpp-mian to form the (bis-dpp-mian)2 Sn (4) species. Compounds 1-4 were characterized by X-ray diffraction.

Cytochrome P450 oxidase SlgO1 catalyzes the biotransformation of tirandamycin C to a new tirandamycin derivative.

In the present study, an Escherichia coli whole cell system with overexpression of a cytochrome P450 oxidase SlgO1 involved in streptolydigin biosynthetic pathway, an E. coli flavodoxin NADP+ oxidoreductase (EcFLDR), and an E. coli flavodoxin A (EcFLDA) were constructed. Biotransformation experiments revealed that SlgO1 can convert tirandamycin C to tirandamycin F, indicating that it can introduce a hydroxyl group into the C-10 position of tirandamycin C. Subsequently, slgO1 was cloned into pSET152AKE vector under the downstream of ermE* promoter, which was, respectively, introduced into Streptomyces sp. SCSIO1666 (tirandamycin B producer), Streptomyces sp. Ju1008 (tirandamycin C producer), and Streptomyces sp. Ju1009 (tirandamycin E producer). A novel tirandamycin derivative tirandamycin L accumulated in the engineered strain Streptomyces sp. Ju1008::slgO1 was isolated and its structure was determined on the basis of nuclear magnetic resonance (NMR) and mass spectrometry. Unlike most of the identified tirandamycins, tirandamycin L possessed a rare C-11-C-12 saturated bond as well as a C-10 ketone moiety. In addition, tirandamycin L showed weaker antibacterial activity. Based on the structure of tirandamycin L, SlgO1 was proposed to be responsible for multiple modifications toward tirandamycin C, including the formation of C-10 hydroxyl and C-11-C-12 saturated bond.

Enhanced Catalytic Activity of Nickel Complexes of an Adaptive Diphosphine-Benzophenone Ligand in Alkyne Cyclotrimerization.

Adaptive ligands, which can adapt their coordination mode to the electronic structure of various catalytic intermediates, offer the potential to develop improved homogeneous catalysts in terms of activity and selectivity. 2,2′-Diphosphinobenzophenones have previously been shown to act as adaptive ligands, the central ketone moiety preferentially coordinating reduced metal centers. Herein, the utility of this scaffold in nickel-catalyzed alkyne cyclotrimerization is investigated. The complex [(p-tolL1)Ni(BPI)] (p-tolL1 = 2,2′-bis(di(para-tolyl)phosphino)-benzophenone; BPI = benzophenone imine) is an active catalyst in the [2 + 2 + 2] cyclotrimerization of terminal alkynes, selectively affording 1,2,4-substituted benzenes from terminal alkynes. In particular, this catalyst outperforms closely related bi- and tridentate phosphine-based Ni catalysts. This suggests a reaction pathway involving a hemilabile interaction of the C=O unit with the nickel center. This is further borne out by a comparative study of the observed resting states and DFT calculations.

Cytotoxic effects of S-(+)-Carvone on selected human cancer cell lines

S-(+)-Carvone (S-CVN), the main constituent of Caraway seed (Carum carvi L.Umbelliferae), has been reported to show significant anticancer and chemopreventive effects against several cancer types. The current study aimed to evaluate the cytotoxic effects of S-CVN on four different human cancer cell lines: ovarian cancer (SW-626), triple negative breast cancer (BT-20), prostate cancer (PC-3) and lymphoma (RAJI). Using MTS proliferation assay, S-CVN showed significant concentration-dependent anti-proliferative effects against the chosen cancer cell lines, with IC50 values of 147,117,199 and 228?M in SW-626, PC-3, BT-20 and RAJI, respectively. Mechanistically, S-CVN with its ?,?-unsaturated carbonyl functionality has the potential to interact with cellular nucleophilic functional groups through Michael’s addition type of reaction. The covalent interaction may explain the observed anti-proliferative activity. To further understand the mechanism of S-CVN cytotoxicity, glutathione (GSH and GSSG) were added to SW-626 cell line as pre- and co-treatments with S-CVN. According to results, the cell viability was enhanced and the cytotoxic effect of S-CVN was extremely decreased using a range of GSH/GSSG concentrations (50 -1000?M). Moreover, the interaction between GSH and S-CVN was further confirmed by using thin layer chromatography (TLC). This is presumably attributed to the fact that the nucleophilic thiol function in GSH interacts with S-CVN ?,?-unsaturated ketone moiety at ?-C. The obtained data suggests that the reactivity of the electrophilic functionality of S-CVN plays a crucial role in its cytotoxicity.

One‐Pot Copper‐Catalyzed Cascade Bicyclization Strategy for Synthesis of 2‐(1H‐Indol‐1‐yl)‐4,5‐dihydrothiazoles and 2‐(1H‐Indol‐1‐yl)thiazol‐5‐yl Aryl Ketones with Molecular Oxygen as an Oxygen Source

AbstractAn atom‐economical method for synthesizing N‐heterocyclic indoles from readily available o‐alkynylphenyl isothiocyanates and propargylamine derivatives is reported. This method involves a copper‐catalyzed cascade bicyclization process consisting of an intramolecular 5‐exo‐dig hydrothiolation reaction and an intramolecular hydroamination reaction and, depending on whether or not molecular oxygen is present, selectively affords Z‐isomers of 2‐(1H‐indol‐1‐yl)‐4,5‐dihydrothiazoles or 2‐(1H‐indol‐1‐yl)thiazol‐5‐yl aryl ketones in satisfactory yields. Mechanistic studies indicate that molecular oxygen acts as the oxygen source for the ketone moiety in the products.magnified image