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TELOMERASE ACTIVATING COMPOUNDS AND METHODS OF USE THEREOF

The present invention is directed to use of a series of com­pounds and compositions comprising the same for activating telomerase and treating diseases, disorders and/or conditions related thereto

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Synthesis, characterization and reactivity of non-heme 1st row transition metal-superoxo intermediates

Metalloenzymes activate dioxygen to generate metal-oxygen adducts that perform a wide range of biological functions. Among the metal-dioxygen intermediates, highly reactive metal-superoxo species are implicated as key intermediates in the catalytic cycle of various enzymatic reactions. Thus, extensive research on model compounds as well as on enzymatic systems has been performed for several decades to understand nature of the metal-superoxo species. In this review, we focus on the synthetic mononuclear metal-superoxo complexes employing copper, iron, nickel and manganese, which are known to exist as metal centers in enzymatic systems. The synthesis, characterization and reactivity studies using synthetic model compounds are investigated to provide mechanistic insights into the catalytic reactions of metalloenzymes. Two different geometries of the mononuclear metal-superoxo intermediates, with end-on and side-on binding modes, are observed that have different spectroscopic features and electronic configurations confirmed by various physicochemical methods. Furthermore, the factors affecting dioxygen activation and reactivity toward organic substrates are revealed by modifying supporting ligand to investigate steric, electronic, hydrogen bonding, solvent and donor atom effects. In the reactivity studies, most of the metal-superoxo species undergo electrophilic reactions including C?H activation, phenol oxidation and oxygen atom transfer. There are a few examples of nucleophilic reactivity of metal-superoxo species, such as aldehyde deformylation. The experimental and theoretical results presented in this review provide us with a better understanding of dioxygen activation and of synthetic strategies using model compounds that can be used to develop efficient bioinspired catalysts.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Multicomponent reactions of phosphines, enynedioates and cinnamaldimines give gamma-lactams with a 1,3,5-hexatriene moiety for facile 6pi electrocyclization: Access to oxindoles, isatins and isoxazolinones

Multicomponent reactions of phosphines, enynedioates and cinnamaldimines generated 3-phosphorus ylide gamma-lactams having a 1,3,5-hexatriene moiety with low activation energy barrier for 6pi electrocyclization, through initial formation of 1,3-dipoles from the alpha(delta’)-Michael addition of phosphines to enynedioates. The reactive 1,3-dipoles underwent addition to cinnamaldimines, lactamization, 6pi electrocyclization and oxidation to give 3-phosphorus ylide oxindoles as platform molecules toward isatins and isoxazolinones. The key step, 6pi electrocyclization, was further examined by a kinetic and a computational study.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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A {Fe(NO)3}10 trinitrosyliron complex stabilized by an N-heterocyclic carbene and the cationic and neutral {Fe(NO)2} 9/10 products of its NO release

In contrast to the instability of XFe(NO)3 and [R 3PFe(NO)3]+, the N-heterocyclic carbene (NHC)-containing trinitrosyliron complex (TNIC) [(IMes)Fe(NO) 3][BF4] (1) [IMes =1,3-bis(2,4,6-trimethylphenyl)imidazol- 2-ylidene] can be readily isolated and manipulated in solution under ambient conditions. Nevertheless, in the presence of thiolates (SR-), this EPR-silent TNIC (denoted {Fe(NO)3}10 in the Enemark-Feltham notation) releases gaseous NO, affording in the case of SR – = SPh- the EPR-active, neutral dinitrosyliron complex (DNIC) (IMes)Fe(SPh)(NO)2 (3, {Fe(NO)2}9). Carbon monoxide enforces a bimolecular reductive elimination of PhSSPh from 3, yielding (IMes)(CO)Fe(NO)2 (2), a reduced {Fe(NO)2} 10 DNIC. The NO released from TNIC 1 in the presence of SPh – could be taken up by the NO-trapping agent [(bme-dach)Fe] 2 [bme-dach = N,N?-bis(2-mercaptoethyl)-1,4-diazacycloheptane] to form the mononitrosyliron complex (MNIC) (bme-dach)Fe(NO). In the absence of SPh-, direct mixing of [(bme-dach)Fe]2 with 1 releases both NO and the NHC with formation of a spin-coupled, diamagnetic {Fe(NO)} 7-{Fe(NO)2}9 complex, [(NO)Fe(bme-dach)Fe(NO) 2][BF4] (4). In 4, the MNIC serves as a bidentate metallodithiolate ligand of Fe(NO)2, forming a butterfly complex in which the Fe-Fe distance is 2.7857(8) A. Thus, 1 is found to be a reliable synthon for [{Fe(NO)2}9]+. The solid-state molecular structures of complexes 1-3 show that all three complexes have a tetrahedral geometry in which the bulky mesitylene substituents of the carbene ligand appear to umbrella the Fe(NO)2L [L = NO (1), CO (2), SPh (3)] motif.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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The tris(4-methylbenzyl) compound Nb(OC6H3Ph2-2,6)2(CH2H4-4Me)3 1 (OC6H3Ph2-2,6 = 2,6-diphenylphenoxide) acts as a catalyst precursor for the hydrogenation of a variety of aryl phosphine ligands.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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C6Me4(C?CH)2-1,2 [Ar(C?CH)2] reacts with PPN[Au(acac)2] (acac = acetylacetonato, PPN = (Ph3P)2N) (2:1) or with [AuCl(SMe2)] and NEt3 (1:2:2) to give PPN[Au{C? CArC?CH}2] (1) or [Au2{mu-Ar(C?C) 2})]n (2), respectively. Dinuclear complexes of general formula [Au2L2{mu-Ar(C?C)2}] can be obtained by reacting 2 with the appropriate ligand L (1:2) [L = tBuNC (3), PMe3 (4), PTo3 (5, To = C6H 4Me-4)] or L2 (1:1) (L2 = Ph 2P(CH2)nPPh2, n = 4 (6), 6 (7)]. The analogous complexes [(AuNHEt2)2{mu-Ar(C?C) 2}] (8) and [{AuC(NHtBu)(NEt2)} 2{mu-Ar(C?C)2}] (9) result from the reactions of Ar(C?CH)2 with PPN[AuCl2] and NHEt2 (1: 2:4) or 3 with an excess of NHEt2, respectively, The reaction of 5 with AgClO4 (2:1) gives the heteropentanuclear “AgAu 4” complex [Ag{(AuPTo3)2{mu- Ar(C?C)2}}2]ClO4 (10). The X-ray crystal structures of 3, 7, 9¡¤1/3CHCl3, and 10¡¤2CHCl 3 have been determined.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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The reduction of the mononitrosyl Re(ii) salt [NMe4] 2[ReCl5(NO)] (1) with zinc in acetonitrile afforded the Re(i) dichloride complex [ReCl2(NO)(CH3CN)3] (2). Subsequent ligand substitution reactions with PCy3, PiPr 3 and P(p-tolyl)3 afforded the bisphosphine Re(i) complexes [ReCl2(NO)(PR3)2(CH3CN)] (3, R = Cy a, iPr b, p-tolyl c) in good yields. The acetonitrile ligand in 3 is labile, permitting its replacement with H2 (1 bar) to afford the dihydrogen Re(i) complexes [ReCl2(NO)(PR3) 2(eta2-H2)] (4, R = Cy a, iPr b). The catalytic activity of 2, 3 and 4 in hydrogen-related catalyses including dehydrocoupling of Me2NH¡¤BH3, dehydrogenative silylation of styrenes, and hydrosilylation of ketones and aryl aldehydes were investigated, with the main focus on phosphine and halide effects. In the dehydrocoupling of Me2NH¡¤BH3, the phosphine-free complex 2 exhibits the same activity as the bisphosphine-substituted systems. In the dehydrogenative silylation of styrenes, 3a and 4a bearing PCy3 ligands exhibit high catalytic activities. Monochloro Re(i) hydrides [Re(Cl)(H)(NO)(PR3)2(CH3CN)] (5, R = Cy a, iPr b) were proven to be formed in the initiation pathway. The phosphine-free complex 2 showed in dehydrogenative silylations even higher activity than the bisphosphine derivatives, which further emphasizes the importance of a facile phosphine dissociation in the catalytic process. In the hydrosilylation of ketones and aryl aldehydes, at least one rhenium-bound phosphine is required to ensure high catalytic activity.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Reaction sequences involving trans-(p-tol)-(Ar3P)2PtCl (Ar = Ph, p-tol), HC?CC?CH, HC?CSiEt3, and oxidative ?CH/HC? cross- or homocoupling (O2, cat. CuCl/TMEDA) give the Cx complexes trans,trans-(p-tol)(Ar3P)2Pt(C?C) nPt(PAr3)2(p-tol) (n = 4, 6), which have been characterized by crystallography and by IR, NMR, and UV-visible spectroscopy.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Mechanism of sulfur transfer from 1,2,4-dithiazolidine-3,5-diones to triphenylphosphines

The mechanism of sulfurization of substituted triphenylphosphines with 4-(3- and 4-substituted)-1,2,4-dithiazolidine-3,5-diones in acetonitrile, dichloromethane, tetrahydrofuran and toluene at 25C was studied. The reaction pathway involves rate-limiting initial nucleophilic attack of the phosphorus at sulfur followed by fast decomposition of the phosphonium intermediate to the corresponding phosphine sulfide, phenylisocyanate and carbonylsulfide. From the Hammett correlations and from the solvent dependency, it was concluded that the transition-state structure is very polar and resembles the zwitter-ionic intermediate. The extent of P-S bond formation and S-S bond cleavage is very similar in the solvents series, but the latter gradually decreases with the decreasing polarity of the solvent. Copyright 2013 John Wiley & Sons, Ltd. The mechanism of sulfurization of substituted triphenylphosphines with 4-(3- and 4-substituted)-1,2,4-dithiazolidine-3,5- diones in acetonitrile, dichloromethane, tetrahydrofuran and toluene at 25C was studied. The reaction pathway involves rate-limiting initial nucleophilic attack of the phosphorus at sulfur followed by fast decomposition of the phosphonium intermediate to the corresponding phosphine sulfide, phenylisocyanate and carbonylsulfide. The transition-state structure is very polar and resembles the zwitter-ionic phosphonium intermediate. Copyright

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Perfluoroalkylation of coordinated ethene in Rh(I) and Ir(I) complexes. Catalytic addition of iodoperfluoroalkanes to ethene

The complexes [M(eta5-Cp?)(eta2-C2H4)2] (M = Rh, Ir) react with iodoperfluoroalkanes to give [M(eta5-Cp?)-(CH2CH2RF)(mu-I)]2 (main product) and [M(eta5-Cp?)-(CH2CH2RF)(mu-I)2M(eta5-Cp?)I] (RF = t-C4F9, M = Ir; RF = c-C6F11, M = Ir, Rh). Similarly, the complexes [M(eta5-Cp?)(eta2-C2H4)(PPh3)] react with iodoperfluoroalkanes to give [M(eta5-Cp?)(CH2CH2RF)I(PPh3)] (M = Ir, RF = t-C4F9, i-C3F7; M = Rh, RF = t-C4F9). Evidence for the generation of the heptafluoroisopropyl carbanion in the reaction of [Ir(eta5-Cp?)(eta2-C2H4)-(PPh3)] with I-i-C3F7 was obtained, which suggests that the reaction is initiated by the transfer of two electrons from the Ir(I) complex to the iodoperfluoroalkane. The iodo-bridged complexes react with PPh3 to give [M(eta5-Cp?)(CH2CH2RF)I(PPh3)] (M = Ir, RF = t-C4F9, c-C6F11; M = Rh, RF = c-C6F11). The complexes [Ir(eta5-Cp?)(CH2CH2RF)I(PPh3)] (RF = c-C6F11, i-C3F7) react with AgOTf to give [Ir(eta5-Cp?)H(eta2-CH2 = CHRF)(PPh3)]OTf. The analogous reaction of [Ir(eta5-Cp?)(CH2CH2-t-C4F9)I(PPh3)] gives CH3CH2-t-C4F9 and [Ir(eta5-Cp?)(eta2-o-C6H4PPh2)]OTf, which reacts with PPh3 to give [Ir(eta5-Cp?)(eta2-o-C6H4PPh2)(PPh3)]OTf. This cyclometalated complex and its analogue [Ir(eta5-Cp?)(eta2-o-C6H4PPh2)(P(p-Tol)3)]OTf are also prepared by the reaction of [Ir(eta5-Cp?)(Me)Cl(PPh3)] with AgOTf and PPh3 or P(p-Tol)3. The derivatives [Ir(eta5-Cp?)(CH2CH2RF)(PPh3)L]OTf (L = CO, RF = c-C6F11, i-C3F7; L = PPh3, RF = i-C3F7) are isolated in the reactions of the Ir hydrido alkene complexes with CO or PPh3. The reactions of [Rh(eta5-Cp?)(CH2CH2RF)I(PR3)] (R = Me, RF = i-C3F7, n-C4F9, t-C4F9; R = Ph, RF = i-C3F7, t-C4F9, c-C6F11) with AgOTf afford unstable triflato complexes that decompose to give CH2 = CHRF, but in the presence of PR3 the complexes [Rh(eta5-Cp?)(CH2CH2RF)(PR3)2]OTf (R = Ph, RF = i-C3F7, t-C4F9, c-C6F11; R = Me, RF = i-C3F7, t-C4F9) were formed. When R = Ph, these complexes are unstable and decompose quantitatively to give [Rh(eta5-Cp?)H(PPh3)2]OTf and CH2 = CHRF. Complexes of the type [M(eta5-Cp?)(eta2-C2H4)2] (M = Rh, Ir) and [Rh(eta5-Cp?)(CH2CH2RF)I(L)] are initiators for the radical addition of IRF to ethene.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate