480-90-0Relevant articles and documents
A new and efficient synthesis of indenone
Zengin,Dastan,Balci
, p. 1993 - 1999 (2001)
Reaction of dichloroketone 2 with NEt3 gave indenone (4) in high yield. Catodic reaction of 2 in the presence of C/Pt electrodes afforded the rearranged product 3 in high yield besides a small amount of chlorohydroxyketone 5. Reaction of rearranged dichloroketone 3 with NEt3 provided indenone (4) as the sole product. The mechanism of these reaction was discussed.
Allylic oxidation of cyclohexene and indene by cis-[Ru(IV)(bpy)2 (py)(O)]2+
Stultz, Laura K.,Huynh, My Hang V.,Binstead, Robert A.,Curry, Maria,Meyer, Thomas J.
, p. 5984 - 5996 (2000)
The kinetics of oxidation of cyclohexene, cyclohexen-1-ol, and indene by cis-[Ru(IV)(bpy)2(py)(O)]2+ (bpy = 2,2'-bipyridine and py = pyridine) have been studied in CH3CN. The reactions are first-order in both Ru(IV)=O2+ and substrate in an initial, rapid stage in which Ru(IV) is reduced to Ru(III). The rate constants are 0.16 ± 0.01, 1.10 ± 0.02, and 5.74 ± 0.74 M-1 s-1 for cyclohexene, cyclohexen-l-ol, and indene, respectively. A k(α,α'-H4)/k(α,α'-D4) kinetic isotope effect of 21 ± 1 is observed for the oxidation of cyclohexene. At a 2:1 ratio of Ru(IV)=O2+ to olefin, the reactions of Ru(IV)=O2+ with either cyclohexene or indene give Ru(II)- NCCH32+ and the 4-electron ketone products, 2-cyclohexen-l-one and indenone, respectively, as identified by GC-MS. As the ratio of cyclohexene to Ru(IV)=O2+ is increased, cyclohexen-l-ol becomes an increasingly competitive product. The mechanisms of these reactions are highly complex. They involve two distinct stages and the formation and subsequent reactions of Ru(III)-substrate bound intermediates.
Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels
Maier,Follmann,Hessler,Kleemann,Hachtel,Fuchs,Weissmann,Linz,Schmidt,L?hn,Schroeter,Wang,Rütten,Strübing
, p. 3650 - 3660 (2015)
Background and Purpose The cation channel transient receptor potential canonical (TRPC) 6 has been associated with several pathologies including focal segmental glomerulosclerosis, pulmonary hypertension and ischaemia reperfusion-induced lung oedema. We set out to discover novel inhibitors of TRPC6 channels and investigate the therapeutic potential of these agents. Experimental Approach A library of potential TRPC channel inhibitors was designed and synthesized. Activity of the compounds was assessed by measuring intracellular Ca2+ levels. The lead compound SAR7334 was further characterized by whole-cell patch-clamp techniques. The effects of SAR7334 on acute hypoxic pulmonary vasoconstriction (HPV) and systemic BP were investigated. Key Results SAR7334 inhibited TRPC6, TRPC3 and TRPC7-mediated Ca2+ influx into cells with IC50s of 9.5, 282 and 226 nM, whereas TRPC4 and TRPC5-mediated Ca2+ entry was not affected. Patch-clamp experiments confirmed that the compound blocked TRPC6 currents with an IC50 of 7.9 nM. Furthermore, SAR7334 suppressed TRPC6-dependent acute HPV in isolated perfused lungs from mice. Pharmacokinetic studies of SAR7334 demonstrated that the compound was suitable for chronic oral administration. In an initial short-term study, SAR7334 did not change mean arterial pressure in spontaneously hypertensive rats (SHR). Conclusions and Implications Our results confirm the role of TRPC6 channels in hypoxic pulmonary vasoregulation and indicate that these channels are unlikely to play a major role in BP regulation in SHR. SAR7334 is a novel, highly potent and bioavailable inhibitor of TRPC6 channels that opens new opportunities for the investigation of TRPC channel function in vivo.
Cyclopentadienones via a Tandem C-Cyclopropylnitrone Cyclization-Cycloreversion Sequence
Erden, Ihsan,G?rtner, Christian,Ma, Jingxiang,Cabrera, Gabriel,Markham, Kate,Azimi, Saeed,Gronert, Scott
, p. 5147 - 5153 (2017)
Aldonitrones derived from spiro[2.4]hepta-4,6-diene-1-carbaldehyde and its benzo analog undergo a tandem uncatalyzed intramolecular cyclopropane–nitrone cyclization-5,6-dihydro-1,2-oxazine cycloreversion to give cyclopentadienones. Similarly, the NH-nitrone generated in situ from spiro[cyclopropane-1,1′-indene]carbaldehyde oxime leads to benzocyclopentadienone (1H-inden-1-one) by the same mechanism. DFT calculations are in favor of a concerted yet highly asynchronous pathway for the cyclizations. Control experiments with the dihydro and tetrahydro derivatives show that the spirocyclopentadiene unit is essential for the success of the reaction, invoking spiroconjugative effects for increased cyclopropane reactivity.
A bioinspired oxoiron(iv) motif supported on a N2S2macrocyclic ligand
Deutscher, Jennifer,Gerschel, Philipp,Warm, Katrin,Kuhlmann, Uwe,Mebs, Stefan,Haumann, Michael,Dau, Holger,Hildebrandt, Peter,Apfel, Ulf-Peter,Ray, Kallol
supporting information, p. 2947 - 2950 (2021/03/24)
A mononuclear oxoiron(iv) complex1-transbearing two equatorial sulfur ligations is synthesized and characterized as an active-site model of the elusive sulfur-ligated FeIVO intermediates in non-heme iron oxygenases. The introduction of sulfur ligands weakens the Fe-O bond and enhances the oxidative reactivity of the FeIVO unit with a diminished deuterium kinetic isotope effect, thereby providing a compelling rationale for nature's use of thecis-thiolate ligated oxoiron(iv) motif in key metabolic transformations.
Mild Darzens Annulations for the Assembly of Trifluoromethylthiolated (SCF3) Aziridine and Cyclopropane Structures
Delost, Michael D.,Njardarson, Jon T.
, p. 6121 - 6125 (2021/08/16)
We report mild new annulation approaches to trisubstituted trifluoromethylthiolated (SCF3) aziridines and cyclopropanes via Darzens inspired protocols. The products of these anionic annulations, rarely studied previously, possess attractive features rendering them valuable building blocks for synthesis platforms. In this study, trisubstituted acetophenone nucleophiles bearing SCF3 and bromine substituents in their α position were shown to undergo [2 + 1] annulations with vinyl ketones and tosyl-protected imines under mild reaction conditions.
Liquid-phase oxidation of olefins with rare hydronium ion salt of dinuclear dioxido-vanadium(V) complexes and comparative catalytic studies with analogous copper complexes
Maurya, Abhishek,Haldar, Chanchal
, (2021/02/26)
Homogeneous liquid-phase oxidation of a number of aromatic and aliphatic olefins was examined using dinuclear anionic vanadium dioxido complexes [(VO2)2(salLH)]? (1) and [(VO2)2(NsalLH)]? (2) and dinuclear copper complexes [(CuCl)2(salLH)]? (3) and [(CuCl)2(NsalLH)]? (4) (reaction of carbohydrazide with salicylaldehyde and 4-diethylamino salicylaldehyde afforded Schiff-base ligands [salLH4] and [NsalLH4], respectively). Anionic vanadium and copper complexes 1, 2, 3, and 4 were isolated in the form of their hydronium ion salt, which is rare. The molecular structure of the hydronium ion salt of anionic dinuclear vanadium dioxido complex [(VO2)2(salLH)]? (1) was established through single-crystal X-ray analysis. The chemical and structural properties were studied using Fourier transform infrared (FT-IR), ultraviolet–visible (UV–Vis), 1H and 13C nuclear magnetic resonance (NMR), electrospray ionization mass spectrometry (ESI-MS), electron paramagnetic resonance (EPR) spectroscopy, and thermogravimetric analysis (TGA). In the presence of hydrogen peroxide, both dinuclear vanadium dioxido complexes were applied for the oxidation of a series of aromatic and aliphatic alkenes. High catalytic activity and efficiency were achieved using catalysts 1 and 2 in the oxidation of olefins. Alkenes with electron-donating groups make the oxidation processes easy. Thus, in general, aromatic olefins show better substrate conversion in comparison to the aliphatic olefins. Under optimized reaction conditions, both copper catalysts 3 and 4 fail to compete with the activity shown by their vanadium counterparts. Irrespective of olefins, metal (vanadium or copper) complexes of the ligand [salLH4] (I) show better substrate conversion(%) compared with the metal complexes of the ligand [NsalLH4] (II).
Modification of MnFe2O4 surface by Mo (VI) pyridylimine complex as an efficient nanocatalyst for (ep)oxidation of alkenes and sulfides
Bouzari, Narges,Bezaatpour, Abolfazl,Babaei, Behnam,Amiri, Mandana,Boukherroub, Rabah,Szunerits, Sabine
, (2021/03/04)
In this current paper, we report a new type of heterogeneous molybdenum (+6) complex, prepared by covalent grafting of cis-dioxo?molybdenum (VI) pyridylimine complex on the surface of MnFe2O4 nanoparticles (NP) and characterized using various physicochemical techniques. The recyclable prepared nanocatalyst was tested for sulfoxidation of sulfides and epoxidation of alkenes under solvent-free condition. The catalyst exhibited high turnover frequency for the oxidization of cyclooctene and cyclohexene (10,850 h?1) and thioanisole and dimethyl sulfide (41,250 h?1). The synthesized catalyst was found highly efficient, retrievable and eco-friendly catalyst for the (ep)oxidation of alkenes and sulfides in excellent yields in a short time. Furthermore, the synthesized nanocatalyst can be reused for four runs without apparent loss of its catalytic activity in the oxidation reaction.
Anchoring of a terpyridine-based Mo(VI) complex on manganese ferrite as a recoverable catalyst for epoxidation of olefins under solvent-free conditions
Fadaei Sarabi, Mahsa,Bezaatpour, Abolfazl,Mahmoudi, Ali
, p. 1597 - 1612 (2021/03/29)
A magnetically separable heterogeneous nanocatalyst was obtained by anchoring a terpyridine-based Mo(VI) complex on modified MnFe2O4 nanoparticles and characterized by Fourier transform infrared (FT-IR), X-ray diffraction (XRD) and diffuse reflectance spectroscopies (DRS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) analysis. The catalytic activity of the supported molybdenum based catalyst was evaluated in the selective epoxidation of various olefins (cyclooctene, limonene, 1-dodecane, 1-heptene, styrene, 1-indene, α-pinene, cyclohexene) with tert-butyl hydroperoxide (TBHP) as an oxidant under solvent-free conditions. This nanocatalyst was easily separated by using an external magnetic field and reused consecutively at least five times with no significant loss in selectivity and catalytic activity. The short reaction time, simple preparation, high conversion, good physicochemical stability and magnetic recycling of the catalysts are beneficial.
Design, synthesis, and biological evaluation of novel sulindac derivatives as partial agonists of PPARγ with potential anti-diabetic efficacy
Huang, Fengyu,Zeng, Zhiping,Zhang, Weidong,Yan, Zhiqiang,Chen, Jiayun,Yu, Liangfa,Yang, Qian,Li, Yihuan,Yu, Hongyu,Chen, Junjie,Wu, Caisheng,Zhang, Xiao-kun,Su, Ying,Zhou, Hu
, (2021/06/22)
Peroxisome proliferator-activated receptor gamma (PPARγ) is a valuable drug target for diabetic treatment and ligands of PPARγ have shown potent anti-diabetic efficacy. However, to overcome the severe side effects of current PPARγ-targeted drugs, novel PPARγ ligands need to be developed. Sulindac, an identified ligand of PPARγ, is widely used in clinic as a non-steroidal anti-inflammatory drug. To explore its potential application for diabetes, we designed and synthesized a series of sulindac derivatives to investigate their structure-activity relationship as PPARγ ligand and potential anti-diabetic effect. We found that meta-substitution in sulindac's benzylidene moiety was beneficial to PPARγ binding and transactivation. Z rather than E configuration of the benzylidene double bond endowed derivatives with the selectivity of PPARγ activation. The indene fluorine is essential for binding and regulating PPARγ. Compared with rosiglitazone, compound 6b with benzyloxyl meta-substitution and Z benzylidene double bond weakly induced adipogenesis and PPARγ-targeted gene expression. However, 6b potently improved glucose tolerance in a diabetic mice model. Unlike rosiglitazone, 6b was devoid of apparent toxicity to osteoblastic formation. Thus, we provided some useful guidelines for PPARγ-based optimization of sulindac and an anti-diabetic lead compound with less side effects.
