- Bioorganometallic chemistry: Biocatalytic oxidation reactions with biomimetic NAD+/NADH co-factors and [Cp*Rh(bpy)H]+ for selective organic synthesis
-
The biocatalytic, regioselective hydroxylation of 2-hydroxybiphenyl to the corresponding catechol was accomplished utilizing the monooxygenase 2-hydroxybiphenyl 3-monooxygenase (HbpA). The necessary natural 1,4-dihydronicotinamde adenine dinucleotide (NAD
- Lutz, Jochen,Hollmann, Frank,Ho, The Vinh,Schnyder, Adrian,Fish, Richard H.,Schmid, Andreas
-
-
Read Online
- In situ formation of H2O2 for P450 peroxygenases
-
An in situ H2O2 generation approach to promote P450 peroxygenases catalysis was developed through the use of the nicotinamide cofactor analogue 1-benzyl-1,4-dihydronicotinamide (BNAH) and flavin mononucleotide (FMN). Final productivity could be enhanced due to higher enzyme stability at low H2O2 concentrations. The H2O2 generation represented the rate-limiting step, however it could be easily controlled by varying both FMN and BNAH concentrations. Further characterization can result in an optimized ratio of FMN/BNAH/O2/biocatalyst enabling high reaction rates while minimizing H2O2-related inactivation of the enzyme.
- Paul, Caroline E.,Churakova, Ekaterina,Maurits, Elmer,Girhard, Marco,Urlacher, Vlada B.,Hollmann, Frank
-
-
Read Online
- The macrocyclic host with four nicotineamide subunits: Hydride transfer from a dihydronicotineamide guest in water
-
A new macrocyclic host has been synthesised from four nicotine amide units linked by two paraxylene groups and two chiral [R,R]-1,2-diaminocyclohexane groups. In this positively charged, tetravalent, D2-symmetric, water soluble host, the two paraxylene groups cooperate to form a hydrophobic cavity where small charged or polar guests can be bound. The host also forms a complex in water with N-benzyldihydronicotineamide in which a hydride ion is transferred from the guest to the host.
- Skog, Klas,Wennerstroem, Olof
-
-
Read Online
- Inhibitors of nicotinamide: N -methyltransferase designed to mimic the methylation reaction transition state
-
Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyses the methylation of nicotinamide to form N′-methylnicotinamide. Both NNMT and its methylated product have recently been linked to a variety of diseases, suggesting a role for the enzyme as a therapeutic target beyond its previously ascribed metabolic function in detoxification. We here describe the systematic development of NNMT inhibitors derived from the structures of the substrates involved in the methylation reaction. By covalently linking fragments of the NNMT substrates a diverse library of bisubstrate-like compounds was prepared. The ability of these compounds to inhibit NNMT was evaluated providing valuable insights into the structural tolerances of the enzyme active site. These studies led to the identification of new NNMT inhibitors that mimic the transition state of the methylation reaction and inhibit the enzyme with activity on par with established methyltransferase inhibitors.
- Van Haren, Matthijs J.,Taig, Rebecca,Kuppens, Jilles,Sastre Tora?o, Javier,Moret, Ed E.,Parsons, Richard B.,Sartini, Davide,Emanuelli, Monica,Martin, Nathaniel I.
-
-
Read Online
- Transfer hydrogenations catalyzed by streptavidin-hosted secondary amine organocatalysts
-
Here, the streptavidin-biotin technology was applied to enable organocatalytic transfer hydrogenation. By introducing a biotin-tethered pyrrolidine (1) to the tetrameric streptavidin (T-Sav), the resulting hybrid catalyst was able to mediate hydride transfer from dihydro-benzylnicotinamide (BNAH) to α,β-unsaturated aldehydes. Hydrogenation of cinnamaldehyde and some of its aryl-substituted analogues was found to be nearly quantitative. Kinetic measurements revealed that the T-Sav:1 assembly possesses enzyme-like behavior, whereas isotope effect analysis, performed by QM/MM simulations, illustrated that the step of hydride transfer is at least partially rate-limiting. These results have proven the concept thatT-Savcan be used to host secondary amine-catalyzed transfer hydrogenations.
- Santi, Nicolò,Morrill, Louis C.,?widerek, Katarzyna,Moliner, Vicent,Luk, Louis Y. P.
-
-
Read Online
- Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation
-
Flavin-dependent halogenases are known to regioselectively introduce halide substituents into aromatic moieties, for example, the indole ring of tryptophan. The process requires halide salts and oxygen instead of molecular halogen in the chemical halogena
- Ismail, Mohamed,Schroeder, Lea,Frese, Marcel,Kottke, Tilman,Hollmann, Frank,Paul, Caroline E.,Sewald, Norbert
-
-
Read Online
- Photocatalytic reduction of artificial and natural nucleotide co-factors with a chlorophyll-like tin-dihydroporphyrin sensitizer
-
An efficient photocatalytic two-electron reduction and protonation of nicotine amide adenine dinucleotide (NAD+), as well as the synthetic nucleotide co-factor analogue N-benzyl-3-carbamoyl-pyridinium (BNAD +), powered by photons in the long-wavelength region of visible light (λirr > 610 nm), is demonstrated for the first time. This functional artificial photosynthetic counterpart of the complete energy-trapping and solar-to-fuel conversion primary processes occurring in natural photosystem I (PS I) is achieved with a robust water-soluble tin(IV) complex of meso-tetrakis(N-methylpyridinium)-chlorin acting as the light-harvesting sensitizer (threshold wavelength of λthr = 660 nm). In buffered aqueous solution, this chlorophyll-like compound photocatalytically recycles a rhodium hydride complex of the type [Cp*Rh(bpy)H]+, which is able to mediate regioselective hydride transfer processes. Different one- and two-electron donors are tested for the reductive quenching of the irradiated tin complex to initiate the secondary dark reactions leading to nucleotide co-factor reduction. Very promising conversion efficiencies, quantum yields, and excellent photosensitizer stabilities are observed. As an example of a catalytic dark reaction utilizing the reduction equivalents of accumulated NADH, an enzymatic process for the selective transformation of aldehydes with alcohol dehydrogenase (ADH) coupled to the primary photoreactions of the system is also demonstrated. A tentative reaction mechanism for the transfer of two electrons and one proton from the reductively quenched tin chlorin sensitizer to the rhodium co-catalyst, acting as a reversible hydride carrier, is proposed.
- Oppelt, Kerstin T.,W??, Eva,Stiftinger, Martin,Sch?fberger, Wolfgang,Buchberger, Wolfgang,Kn?r, Günther
-
-
Read Online
- Investigating the Structure-Reactivity Relationships Between Nicotinamide Coenzyme Biomimetics and Pentaerythritol Tetranitrate Reductase
-
Ene reductases (ERs) are attractive biocatalysts in terms of their high enantioselectivity and expanded substrate scope. Recent works have proved that synthetic nicotinamide coenzyme biomimetics (NCBs) can be used as easily accessible alternatives to natural cofactors in ER-catalyzed reactions. However, the structure-reactivity relationships between NCBs and ERs and influence factors are still poorly understood. In this study, a series of C-5 methyl modified NCBs were synthesized and tested in the PETNR-catalyzed asymmetric reductions. The physicochemical properties of these NCBs including electrochemical properties, stability, and kinetic behavior were studied in detail. The results showed that hydrophobic interaction caused by the introduced methyl group contributed to the stabilization of binding conformation in enzyme active site, resulting in comparable catalytic activity with that of NADPH. Molecular dynamics and steered molecular dynamics simulations were further performed to explain the binding mechanism between PETNR and NCBs, which revealed that stable catalytic conformation, appropriate donor-acceptor distance and angle, as well as free dissociation energy are important factors affecting the activity of NCBs. (Figure presented.).
- Tan, Zhuotao,Han, Yaoying,Fu, Yaping,Zhang, Xiaowang,Xu, Mengjiao,Na, Qi,Zhuang, Wei,Qu, Xudong,Ying, Hanjie,Zhu, Chenjie
-
supporting information
p. 103 - 113
(2021/10/07)
-
- COMPOUNDS FOR PROMOTING FOLLICLE MATURATION
-
Some analogues (eg. 3-carbamoyl-1-(tetrahydro-2H-pyran-4-yl)pyridin-1-ium, 3- carboxy-1-isopropylpyridin-1-ium, 1-benzyl-3-carbamoylpyridin-1-ium, 3-carbamoyl-1- methylpyridin-1-ium and cyclopamine) are disclosed to treat female infertility as the compounds increase the percentage of primary follicles relative to primordial follicles compared to control samples.
- -
-
Page/Page column 17
(2021/07/17)
-
- The visible-light-driven transfer hydrogenation of nicotinamide cofactors with a robust ruthenium complex photocatalyst
-
The highly efficient regeneration of nicotinamide cofactors has been successfully achieved with a quantum yield (Φ) of 7.9 × 10-3via photocatalytic transfer hydrogenation in the presence of the ruthenium complex Ru(tpy)(biq)Cl2 (where tpy = 2,2′:6′,2′′-terpyridine and biq = 2,2′-bisquinoline). The photocatalytic system is not only highly efficient but also tolerant to amino acid residues. The combination of this photocatalyst with glutamate dehydrogenase enabled the controllable and efficient synthesis of l-glutamate to be realized. A mechanism involving light-induced ligand exchange, decarboxylation and hydride transfer has been proposed. Kinetic isotope experiments revealed that the decarboxylation of [Ru(tpy)(biq)HCOO]+ to [Ru(tpy)(biq)H]+ was the rate-determining step with a small apparent activation energy of 3.2 ± 0.4 kcal mol-1. The hydricity of [Ru(tpy)(biq)H]+ was estimated, via reaction equilibrium, to be 40 ± 3 kcal mol-1
- Chen, Fushan,Deng, Li,Dong, Wenjin,Tang, Jie,Xian, Mo,Zhao, Lijun
-
p. 2279 - 2287
(2020/04/20)
-
- Photoenzymatic epoxidation of styrenes
-
Two-component-diffusible-flavomonooxygenases are versatile biocatalysts for selective epoxidation-, hydroxylation- or halogenation reactions. Their complicated molecular architecture can be simplified using photochemical regeneration of the catalytically
- Van Schie, Morten M. C. H.,Paul, Caroline E.,Arends, Isabel W. C. E.,Hollmann, Frank
-
supporting information
p. 1790 - 1792
(2019/02/12)
-
- Biocatalytic C=C Bond Reduction through Carbon Nanodot-Sensitized Regeneration of NADH Analogues
-
Light-driven activation of redox enzymes is an emerging route for sustainable chemical synthesis. Among redox enzymes, the family of Old Yellow Enzyme (OYE) dependent on the nicotinamide adenine dinucleotide cofactor (NADH) catalyzes the stereoselective reduction of α,β-unsaturated hydrocarbons. Here, we report OYE-catalyzed asymmetric hydrogenation through light-driven regeneration of NADH and its analogues (mNADHs) by N-doped carbon nanodots (N-CDs), a zero-dimensional photocatalyst. Our spectroscopic and photoelectrochemical analyses verified the transfer of photo-induced electrons from N-CDs to an organometallic electron mediator (M) for highly regioselective regeneration of cofactors. Light triggered the reduction of NAD+ and mNAD+s with the cooperation of N-CDs and M, and the reduction behaviors of cofactors were dependent on their own reduction peak potentials. The regenerated cofactors subsequently delivered hydrides to OYE for stereoselective conversions of a broad range of substrates with excellent biocatalytic efficiencies.
- Kim, Jinhyun,Lee, Sahng Ha,Tieves, Florian,Choi, Da Som,Hollmann, Frank,Paul, Caroline E.,Park, Chan Beum
-
supporting information
p. 13825 - 13828
(2018/09/11)
-
- Slow generation of hydrogen sulfide from sulfane sulfurs and NADH models
-
Here we report the model studies of the reactions between NADH models (using HEH and BNAH) and sulfane sulfurs (using polysulfides). Such reactions could lead to the oxidation of NADH models and the production of hydrogen sulfide (H2S). Kinetics of the reaction between BNAH and elemental sulfur S8were determined in ethanol and the second-order rate constant was found to be 0.074?M?1?min?1(at 37?°C) suggesting this is a slow process.
- Peng, Bo,Liu, Chunrong,Li, Zhen,Day, Jacob J.,Lu, Yun,Lefer, David J.,Xian, Ming
-
supporting information
p. 542 - 545
(2017/01/17)
-
- Pyridinium oxidations of benzyl alcohol under microwave-assisted retro-ene conditions
-
Benzyl alcohol is oxidized to benzaldehyde when heated in sulfolane in the presence of N-benzylnicotinamide and N-benzylpyridinium salts. The oxidation is accelerated in the presence microwaves. Oxidations with related pyridiniums suggest that these oxidations could occur via retro-ene reactions.
- Jensen, Anton W.,Moore, John M.,Kimble, MaryEllen V.,Ausmus, Alex P.,Dilling, Wendell L.
-
supporting information
p. 5636 - 5638
(2016/11/28)
-
- Steric Effects on the Primary Isotope Dependence of Secondary Kinetic Isotope Effects in Hydride Transfer Reactions in Solution: Caused by the Isotopically Different Tunneling Ready State Conformations?
-
The observed 1° isotope effect on 2° KIEs in H-transfer reactions has recently been explained on the basis of a H-tunneling mechanism that uses the concept that the tunneling of a heavier isotope requires a shorter donor-acceptor distance (DAD) than that of a lighter isotope. The shorter DAD in D-tunneling, as compared to H-tunneling, could bring about significant spatial crowding effect that stiffens the 2° H/D vibrations, thus decreasing the 2° KIE. This leads to a new physical organic research direction that examines how structure affects the 1° isotope dependence of 2° KIEs and how this dependence provides information about the structure of the tunneling ready states (TRSs). The hypothesis is that H- and D-tunneling have TRS structures which have different DADs, and pronounced 1° isotope effect on 2° KIEs should be observed in tunneling systems that are sterically hindered. This paper investigates the hypothesis by determining the 1° isotope effect on α- and β-2° KIEs for hydride transfer reactions from various hydride donors to different carbocationic hydride acceptors in solution. The systems were designed to include the interactions of the steric groups and the targeted 2° H/D's in the TRSs. The results substantiate our hypothesis, and they are not consistent with the traditional model of H-tunneling and 1° /2° H coupled motions that has been widely used to explain the 1° isotope dependence of 2° KIEs in the enzyme-catalyzed H-transfer reactions. The behaviors of the 1° isotope dependence of 2° KIEs in solution are compared to those with alcohol dehydrogenases, and sources of the observed "puzzling" 2° KIE behaviors in these enzymes are discussed using the concept of the isotopically different TRS conformations. (Figure Presented).
- Maharjan, Binita,Raghibi Boroujeni, Mahdi,Lefton, Jonathan,White, Ormacinda R.,Razzaghi, Mortezaali,Hammann, Blake A.,Derakhshani-Molayousefi, Mortaza,Eilers, James E.,Lu, Yun
-
p. 6653 - 6661
(2015/06/08)
-
- Discrimination of redox-responsible biomolecules by a single molecular sensor
-
A new application of a fluorescent sensor (PyDPA) for the discrimination of redox-responsible molecules is reported. Nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD +/NADP+) and flavin mononucleotid
- Oh, Jinrok,Hong, Jong-In
-
supporting information
p. 1210 - 1213
(2013/05/09)
-
- Biomimetic hydrogenation: A reusable NADH co-enzyme model for hydrogenation of α,β-epoxy ketones and 1,2-diketones
-
A biomimetic method has been developed to transform α,β-epoxy ketones or 1,2-diketones into corresponding β-hydroxy ketones or α-hydroxy ketones using a catalytic amount of BNAH or BNA +Br-. The regeneration of BNAH or BNA+Br - is achieved by a mixture of HCOOH/Et3N. A radical mechanism is proposed to explain these observations.
- Huang, Qiang,Wu, Ji-Wei,Xu, Hua-Jian
-
supporting information
p. 3877 - 3881
(2013/07/05)
-
- Facile oxidation of leucomethylene blue and dihydroflavins by artemisinins: Relationship with flavoenzyme function and antimalarial mechanism of action
-
The antimalarial drug methylene blue (MB) affects the redox behaviour of parasite flavin-dependent disulfide reductases such as glutathione reductase (GR) that control oxidative stress in the malaria parasite. The reduced flavin adenine dinucleotide cofactor FADH2 initiates reduction to leucomethylene blue (LMB), which is oxidised by oxygen to generate reactive oxygen species (ROS) and MB. MB then acts as a subversive substrate for NADPH normally required to regenerate FADH2 for enzyme function. The synergism between MB and the peroxidic antimalarial artemisinin derivative artesunate suggests that artemisinins have a complementary mode of action. We find that artemisinins are transformed by LMB generated from MB and ascorbic acid (AA) or N-benzyldihydronicotinamide (BNAH) in situ in aqueous buffer at physiological pH into single electron transfer (SET) rearrangement products or two-electron reduction products, the latter of which dominates with BNAH. Neither AA nor BNAH alone affects the artemisinins. The AA-MB SET reactions are enhanced under aerobic conditions, and the major products obtained here are structurally closely related to one such product already reported to form in an intracellular medium. A ketyl arising via SET with the artemisinin is invoked to explain their formation. Dihydroflavins generated from riboflavin (RF) and FAD by pretreatment with sodium dithionite are rapidly oxidised by artemisinin to the parent flavins. When catalytic amounts of RF, FAD, and other flavins are reduced in situ by excess BNAH or NAD(P)H in the presence of the artemisinins in the aqueous buffer, they are rapidly oxidised to the parent flavins with concomitant formation of twoelectron reduction products from the artemisinins; regeneration of the reduced flavin by excess reductant maintains a catalytic cycle until the artemisinin is consumed. In preliminary experiments, we show that NADPH consumption in yeast GR with redox behaviour similar to that of parasite GR is enhanced by artemisinins, especially under aerobic conditions. Recombinant human GR is not affected. Artemisinins thus may act as antimalarial drugs by perturbing the redox balance within the malaria parasite, both by oxidising FADH2 in parasite GR or other parasite flavoenzymes, and by initiating autoxidation of the dihydroflavin by oxygen with generation of ROS. Reduction of the artemisinin is proposed to occur via hydride transfer from LMB or the dihydroflavin to O1 of the peroxide. This hitherto unrecorded reactivity profile conforms with known structure-activity relationships of artemisinins, is consistent with their known ability to generate ROS in vivo, and explains the synergism between artemisinins and redox-active antimalarial drugs such as MB and doxorubicin. As the artemisinins appear to be relatively inert towards human GR, a putative model that accounts for the selective potency of artemisinins towards the malaria parasite also becomes apparent. Decisively, ferrous iron or carbon-centered free radicals cannot be involved, and the reactivity described herein reconciles disparate observations that are incompatible with the ferrous iron-carbon radical hypothesis for antimalarial mechanism of action. Finally, the urgent enquiry into the emerging resistance of the malaria parasite to artemisinins may now in one part address the possibilities either of structural changes taking place in parasite flavoenzymes that render the flavin cofactor less accessible to artemisinins or of an enhancement in the ability to use intra-erythrocytic human disulfide reductases required for maintenance of parasite redox balance.
- Haynes, Richard K.,Chan, Wing-Chi,Wong, Ho-Ning,Li, Ka-Yan,Wu, Wai-Keung,Fan, Kit-Man,Sung, Herman H. Y.,Williams, Ian D.,Prosperi, Davide,Melato, Sergio,Coghi, Paolo,Monti, Diego
-
experimental part
p. 1282 - 1299
(2011/01/04)
-
- Negative kinetic temperature effect on the hydride transfer from NADH analogue BNAH to the radical cation of N-benzylphenothiazine in acetonitrile
-
The reaction rates of 1-(p-substituted benzyl)-1,4-dihydronicotinamide (G-BNAH) with N-benzylphenothiazine radical cation (PTZ?+) in acetonitrile were determined. The results show that the reaction rates (k obs) decreased from 2.80 × 107 to 2.16 × 107 M-1 s-1 for G = H as the reaction temperature increased from 298 to 318 K. The activation enthalpies of the reactions were estimated according to Eyring equation to give negative values (-3.4 to -2.9 kcal/mol). Investigation of the reaction intermediate shows that the charge-transfer complex (CT-complex) between G-BNAH and PTZ ?+ was formed in front of the hydride transfer from G-BNAH to PTZ?+. The formation enthalpy of the CT-complex was estimated by using the Benesi-Hildebrand equation to give the values from -6.4 to -6.0 kcal/mol when the substituent G in G-BNAH changes from CH3O to Br. Detailed thermodynamic analyses on each elementary step in the possible reaction pathways suggest that the hydride transfer from G-BNAH to PTZ?+ occurs by a concerted hydride transfer via a CT-complex. The effective charge distribution on the pyridine ring in G-BNAH at the various stages-the reactant G-BNAH, the charge-transfer complex, the transition-state, and the product G-BNA+-was estimated by using the method of Hammett-type linear free energy analysis, and the results show that the pyridine ring carries relative effective positive charges of 0.35 in the CT-complex and 0.45 in the transition state, respectively, which indicates that the concerted hydride transfer from G-BNAH to PTZ?+ was practically performed by the initial charge (-0.35) transfer from G-BNAH to PTZ?+ and then followed by the transfer of hydrogen atom with partial negative charge (-0.65). It is evident that the present work would be helpful in understanding the nature of the negative temperature effect, especially on the reaction of NADH coenzyme with the drug phenothiazine in vivo.
- Zhu, Xiao-Qing,Zhang, Jian-Yu,Cheng, Jin-Pei
-
p. 7007 - 7015
(2007/10/03)
-
- Method for treating fibrotic diseases or other indications IIIC
-
Provided is a method of treating or ameliorating certain fibrotic diseases or other indications in an animal, including a human, comprising administering an effective amount of a compound of the formula I: Y—Ar⊕·X— wherein: a. Ar is a five or s
- -
-
-
- SIMPLE PREPARATIONS OF C-4-TERT-BUTYLATED NADH/NAD+ ANALOGS
-
The addition of tert-butyl Grignard reagent to the 1-benzyl-3-carbamoylpyridinium salt (1) gives a mixture C-4-(2), C-6-(3), and C-2-tert-butylated dihydronicotinamides (4) in which the desired 1,4-isomer predominates.Stable cristalline 1-benzyl-4-tert-butyl-1,4-dihydronicotinamide (2) can be easily isolated.Oxidation of the product with the 1-benzyl-3-cyanoquinolinium ion (6) was found to be strongly solvent-dependent.In acetonitrile, exclusive hydride transfer gives the corresponding C-4-tert-butylated pyridinium ion (5).In methanol, an interesting tert-butyl transfer from 1,4-dihydronicotinamide (2) to quinolinium (6) occurs competitively, and predominates in the presence of a catalytic amount of formic acid; the resulting C-4-tert-butylated 1,4-dihydroquinoline derivative (8) can be readily isolated.
- Anne, Agnes
-
p. 2331 - 2337
(2007/10/02)
-
- Addition of Cyanide Ion to Nicotinamide Cations in Acetonitrile. Formation of Non-productive Charge-transfer Complexes
-
The mixing of equal volumes of 0.2 mmol dm-3 1-benzylnicotinamide ion and 2 mmol dm-3 cyanide ion results in the immediate formation of a transient absorption band at 375 nm which can be ascribed to a charge-transfer complex.This com
- Engbersen, Johan F. J.,Koudijs, Arie,Sleiderink, Hedwig M.,Franssen, Maurice C. R.
-
-
- Marcus Theory of Hydride Transfer from an Anionic reduced Deazaflavin to NAD+ Analogues
-
Eighteen rate constants, kij for hydride transfer from the conjugate base of 1,5-dihydro-3,10-dimethyl-5-diazaisoalloxazine to a variety of pyridinium, quinolinium, phenanthridinium, and acridinium ions have been determined. (All the oxidizing agents can be regarded as analogues of NAD+.) The kij values span 7 powers of 10 and the corresponding equilibrium constants, Kij, span more than 13 powers of 10.For reactions with ΔG0 near zero, the kij values are close to those given by modified Marcus theory (ref 10).However, with more negative ΔG0 values, the observed kij increase more strogly than the calculated values.Agreement can be produced by making the standard free energy of precursor complex formation, symbolized WT +- here, to indicate that it applies to reactants of opposite charge, a linear function of ΔG0, and treating the slope and interrcept of the linear relation as adjustable parameters.The best fit is obtained with WT+-(in kJ*mol-1)=-9.4+0.11ΔG0.An avarage discrepancy between calculated and observed ln kij values of 0.5 is achieved, which is a good as the overall fit achieved for hydride transfer from neutral NADH analogues to NAD+ analogues (ref 10).The form and the parameterization of Wf are shown to be a physically reasonable approximation for reactions with ΔG00.These results strengthen the conclusion (ref 10) that a wide range of hydride transfer rates can be quantitavely understood without introducing high-energy metastable intermediates (radicals and radical ions).
- Lee, In-Sook Han,Ostovic, Drazen,Kreevoy, Maurice
-
p. 3989 - 3993
(2007/10/02)
-
- Reactivity of a Cyclic α-Bromoiminium Bromide towards Nucleophiles
-
Piperidine-pyrrolidine ring contraction of 1-piperideinium bromide (1) was observed by reaction with aqueous bases, sodium methoxide, phenylhydrazine, (S)-1-phenylethylamine and sodium borohydride, whereas diazomethane addition mainly gave pyrrolopyridine derivative 8.Some stereochemical features of these reactions have been investigated. 1 gave back bromine under suitable conditions.
- Donati, Donato,Fusi, Stefania,Macripo, Maria Adelaide,Ponticelli, Fabio
-
p. 481 - 483
(2007/10/02)
-
- Regioselectivity of Hydride Transfer to and between NAD+ Analogues
-
The reaction of 1-methyl- or 1-benzylquinolinium compounds, also bearing an electron-withdrawing substituent in the 3-position, with NaBH4, gives mixtures of the corresponding 1,2-dihydroquinolines and 1,4-dihydroquinolines in which the 1,2-dihydro derivatives usually predominate.The 1,2-derivatives can be isolated.The 1,2-isomers react with the quinolinium salts, giving the 1,4-isomers and regenerating quinolinium salts.This bimolecular isomerization can be used to convert a mixture of isomers to the 1,4-isomer on a preparative scale. 3-Cyano-1,2-dihydro-1-methylquinoline also isomerizes to the 1,2-isomer in the crystalline solid.The major first product of NaBH4 reduction of 3-(aminocarbonyl)-1-benzylpyridinium ion is the 1,6-dihydro derivative.This also isomerizes to the 1,4-dihydro compound in the presence of the pyridinium ion.Reduction of quinolinium derivatives with Na2S2O4 or a dihydropyridine directly produces the 1,4-isomer predominantly.Reduction of 3-(aminocarbonyl)-1-benzylpyridinium ion with Na2S2O4 in D2O gives the 1,4-dihydro derivative, but 8percent of the deuterium is in the 2-position; presumably by reversible isomerization.This deuterium redistribution may have important consequences for the interpretation of isotope effects.
- Roberts, R. M. G.,Ostovic, D.,Kreevoy, M. M.
-
p. 2053 - 2056
(2007/10/02)
-
- Kinetics and Mechanism of the Reaction of 5-Nitroisoquinolinium Cations with 1,4-Dihydronicotinamides
-
The kinetics of the reduction of 2-methyl- (7) and 2-(Z-benzyl)-5-nitroisoquinolinium cations (2) by 1-(X-benzyl)-1,4-dihydronicotinamides (1) to give the corresponding 1,2-dihydro-5-nitroisoquinolines have been studied in 20percent acetonitrile-80percent
- Bunting, John W.,Sindhuatmadja, Shinta
-
p. 4211 - 4219
(2007/10/02)
-