Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IMINES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed2004

Studies on the reactions between daptomycin and glyceraldehyde.

The objectives of this project were to determine the reaction pathways of daptomycin in the presence of glyceraldehyde in acidic solutions, and to quantitate the kinetics of the major pathways. In the presence of glyceraldehyde (pH range 1-7 at 25 to 60 degrees C), daptomycin formed two major products separable by RP-HPLC. The products were identified using UV spectroscopy, fluorimetry, mass spectrometry, and 2D-1H NMR. The reaction scheme involved the reversible formation of imine and anilide derivatives. Carbinolamine was believed to be a common intermediate in formation pathways of both products. The carbinolamine intermediate underwent either acid catalyzed dehydration resulting in imine formation or intramolecular hydrogen bonding and bond cleavage giving rise to anilide formation. In mild acid conditions, both products reversed to daptomycin. The reaction between daptomycin and glyceraldehyde was first-order with respect to both reactants. In a pH range of 1-7, the imine formation rate was pH dependent with a maximum rate at approximate pH values of 3-4. The observed pH dependence was consistent with the pH dependence of typical amine-aldehyde reactions.

Anilides↗
PubMed2005

Oxidation of Zn(N2S2) complexes to disulfonates: relevance to zinc-finger oxidation under oxidative stress.

A series of Zn(N2S2) complexes has been prepared, and characterized. They have different nitrogen donors such as, either two amidates, two amines, two imines or one amidate and one imine. A bis-amidato dithiolato complex has been structurally characterized by single crystal X-ray diffraction analysis, and exhibits a distorted tetrahedral structure. Oxidation of all these complexes with dioxirane or anhydrous H2O2 results in the formation of a unique product, the disulfonate species. Most often, zinc was found to be released during the course of the oxidation. The bis-imine/bis-sulfonate species is the only one to retain zinc. This complex was crystallized with two pyridine molecules. Its crystal structure reveals a distorted octahedral environment around the zinc cation.

Journal Article↗
PubMed2003

Behaviors and mechanisms of copper adsorption on hydrolyzed polyacrylonitrile fibers.

Polyacrylonitrile fiber (PANF) was hydrolyzed in a solution of sodium hydroxide and the hydrolyzed polyacrylonitrile fiber (HPANF) was used as an adsorbent to remove copper ions from aqueous solution. Scanning electron microscopy (SEM) showed that the hydrolysis process made the surface of HPANF rougher than that of PANF. Fourier transform infrared (FTIR) spectroscopy revealed that the HPANF contained conjugated imine (-Cz=Nz-) sequences. Batch adsorption results indicated that the HPANF was very effective in adsorbing copper, and the adsorption equilibrium could be reached within 10-20 min. Atomic force microscopy (AFM) showed that some aggregates formed on the surface of the HPANF after copper ion adsorption and the average surface roughness (R(a)) value of the HPANF changed from 0.363 to 3.763 nm due to copper adsorption. FTIR analysis indicated that copper adsorption caused a decrease of the light adsorption intensity of the imine (-Cz=Nz-) groups at 1573 and 1406 cm(-1) wavenumbers, and X-ray photoelectron spectroscopy (XPS) showed that the binding energy (BE) of some of the nitrogen atoms in the HPANF increased to a greater value due to copper adsorption. The FTIR and XPS results suggest that the adsorption of copper ions to the HPANF is attributed to the imine groups on the surface of the HPANF.

Journal Article↗
PubMed1998

Synthesis and antiviral activity of prodrugs of the nucleoside 1-[2',3'-dideoxy-3'-C-(hydroxymethyl)-beta-D-erythropentofuranosyl] cytosine.

The synthesis and antiviral evaluation of 21 prodrugs of 1-[2',3'-dideoxy-3'-C-(hydroxymethyl)-beta-D-erythropentofuranosyl ] cytosine 1 is reported. Cytosine N4-imine analogues were prepared by condensation of 1 with selected formamide dimethyl acetals. Amino acid substituted prodrugs were prepared from 1 or imine prodrug 2 by coupling with either N-tert-butoxycarbonyl (t-Boc)-L-valine or N-t-Boc-L- phenylalanine in the presence of dicyclohexycarbodiimide (DCC) and 4-dimethylaminopyridine (4-DMAP). Deprotection of the t-Boc protecting group was achieved with trifluoroacetic acid (TFAA) in methylene chloride. Cytosine N4-amide analogues were prepared by reaction of 1 with appropriate anhydrides in aqueous dioxane. Triacylated analogue 22 was prepared by reaction of 1 with four equivalents of benzoyl chloride in pyridine. Prodrugs were evaluated for activity against duck hepatitis B virus, herpes simplex virus types 1 and 2, human cytomegalovirus, and human immunodeficiency virus. A number of analogues were found comparable in activity to 1 with the cytosine N4-imine series more active than the amino acid substituted and cytosine N4-amide prodrugs. Slight to moderate cellular toxicity was observed with some analogues.

Antiviral Agents↗
PubMed1995

Expression, purification, and characterization of Escherichia coli dihydrodipicolinate reductase.

Dihydrodipicolinate reductase catalyzes the NAD(P)H-dependent reduction of the carbon-carbon double bond of the alpha,beta-unsaturated cyclic imine dihydrodipicolinate to form the cyclic imine tetrahydrodipicolinate. The enzyme is a component of the bacterial biosynthetic pathway forming L-lysine and diaminopimelate from L-aspartate. The gene encoding dihydrodipicolinate reductase, dapB, has been cloned and sequenced from Escherichia coli (Bouvier et al., 1984), and we have used this sequence information to generate an expression vector containing the dapB gene. Expression and purification of dihydrodipicolinate reductase to homogeneity have allowed us to characterize the kinetics, stereochemistry, and chemical mechanism of the enzymatic reaction. The kinetic mechanism is ordered, with reduced nucleotide binding preceding dihydrodipicolinate binding and presumably with tetrahydrodipicolinate dissociating prior to oxidized nucleotide release. The enzyme has a unique nucleotide specificity, with NADH being twice as effective as NADPH as a reductant. The enzyme catalyzes the stereospecific transfer of the 4R hydrogen atom of the reduced nucleotide, as a hydride ion, to the 4 position of dihydrodipicolinate. These results allow us to propose a chemical mechanism for the reaction catalyzed by dihydrodipicolinate reductase involving hydride transfer to the beta carbon of the unsaturated imine. The resonance-stabilized C3 carbanion is protonated to generate the reduced product, tetrahydrodipicolinate.

Chromatography, Gel↗
PubMed2000

Structure-activity relations in the oxidation of phenethylamine analogues by recombinant human liver monoamine oxidase A.

The interaction of recombinant human liver monoamine oxidase A (MAO A) with a series of phenethylamine substrate analogues has been investigated by steady-state and stopped-flow kinetic techniques. Substrate analogues with para substituents exhibit large deuterium kinetic isotope effect on k(cat), on k(cat)/K(m), and on the limiting rate of enzyme reduction in reductive half-reaction experiments. These kinetic isotope effect values range from 5 to 10 with the exception of tyramine, which exhibited smaller steady-state isotope effects (2.3-3.5) than that observed on the rate of flavin reduction (6.9). The stopped-flow data show that imine release from the reduced enzyme is slower than the rate of catalytic turnover. Phenethylamine oxidation by MAO A can be described as the C-H bond cleavage step being rate limiting in catalysis and with oxygen reacting with the reduced enzyme-imine complex. In the case of tyramine, the product release from the oxidized enzyme-imine complex contributes to the rate limitation in catalysis. The binding affinities of a series of para-substituted phenethylamine analogues to MAO A show an increase in affinity of the deprotonated amine with increasing van der Waals volume of the substituent. The limiting rate of enzyme reduction decreases with increasing van der Waals volume of the substituent in a linear manner with no observable electronic contribution as observed previously with benzylamine reduction of MAO A [Miller, J. R., and Edmondson, D. E. (1999) Biochemistry 38, 13670-13683]. Examination of side chain analogues of phenethylamine show 3-phenylpropylamine to be oxidized 2.5-fold more slowly and bound 75-fold more tightly than phenethylamine. 4-Phenylbutylamine is not a substrate for MAO A but is a good competitive inhibitor with a K(i) value of 31 +/- 5 microM. Analysis of the effect of alkyl side chain alterations on binding affinities of a series of arylalkylamine analogues taken from this study and from the literature show a linear correlation with the Taft steric value (E(s)) of the side chain. These results suggest that the binding site for the aryl ring is identical for phenethylamine and for benzylamine analogues and that steric interactions of the alkyl side chain with the enzyme strongly contribute to the binding affinities of a series of reversible inhibitors of MAO A.

Flow Injection Analysis↗
PubMed1988

13C NMR studies of methylene and methine carbons of substrate bound to a 280,000-dalton protein, porphobilinogen synthase.

13C NMR has been used to observe the equilibrium complex of [5,5-2H,5-13C]-5-aminolevulinate [( 5,5-2H,5-13C]ALA) bound to porphobilinogen (PBG) synthase (5-aminolevulinate dehydratase), a 280,000-dalton protein. [5,5-2H,5-13C]ALA (chemical shift 46.9 ppm in D2O) was prepared from [5-13C]ALA through enolization in deuteriated neutral potassium phosphate buffer. In the PBG synthase reaction [5,5-2H,5-13C]ALA forms [2,11,11-2H,2,11-13C]PBG (chemical shifts 116.2 ppm for C2 and 34.2 ppm for C11 in D2O). For the complex formed between [5,5-2H,5-13C]ALA and methyl methanethiosulfonate (MMTS) modified PBG synthase, which does not catalyze PBG formation but can form a Schiff base adduct, the chemical shift of 44.2 ppm (line width 92 Hz) identifies an imine structure as the predominant tautomeric form of the Schiff base. By comparison to model compounds, the stereochemistry of the imine has been deduced; however, the protonation state of the imine nitrogen remains unresolved. Reconstitution of the MMTS-modified enzyme-Schiff base complex with Zn(II) and 2-mercaptoethanol results in the holoenzyme-bound equilibrium complex; this complex contains predominantly enzyme-bound PBG, and spectra reveal two peaks from bound PBG and two from free PBG. For bound PBG, C2 is -2.8 ppm from the free signal and C11 is +2.6 ppm from the free signal; the line widths of the bound signals are 55 and 75 Hz, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminolevulinic Acid↗
PubMed1988

Use of primary deuterium and 15N isotope effects to deduce the relative rates of steps in the mechanisms of alanine and glutamate dehydrogenases.

We have used deuterium and 15N isotope effects to study the relative rates of the steps in the mechanisms of alanine and glutamate dehydrogenases. The proposed chemical mechanisms for these enzymes involve carbinolamine formation, imine formation, and reduction of the imine to the amino acid [Grimshaw, C.E., Cook, P.F., & Cleland, W.W. (1981) Biochemistry 20, 5655; Rife, J.E., & Cleland, W.W. (1980) Biochemistry 19, 2328]. These steps are almost equally rate limiting for V/Kammonia with alanine dehydrogenase, while with glutamate dehydrogenase carbinolamine formation, imine formation, and release of glutamate after hydride transfer provide most of the rate limitation of V/Kammonia. Release of oxidized nucleotide is largely rate limiting for Vmax for both enzymes. When beta-hydroxypyruvate replaces pyruvate, or 3-acetylpyridine NADH (Acpyr-NADH) or thio-NADH replaces NADH with alanine dehydrogenase, nucleotide release no longer limits Vmax, and hydride transfer becomes more rate limiting. With glutamate dehydrogenase, replacement of alpha-ketoglutarate by alpha-ketovalerate makes hydride transfer more rate limiting. Use of Acpyr-NADPH has a minimal effect with alpha-ketoglutarate but causes an 8-fold decrease in Vmax with alpha-ketovalerate, with hydride transfer the major rate-limiting step. In contrast, thio-NADPH with either alpha-keto acid causes carbinolamide formation to become almost completely rate limiting. These studies show the power of multiple isotope effects in deducing details of the chemistry and changes in rate-limiting step(s) in complicated reaction mechanisms such as those of alanine and glutamate dehydrogenases.

Alanine Dehydrogenase↗
PubMed1988

Mechanism-based inactivation of rabbit muscle phosphoglucomutase by nojirimycin 6-phosphate.

Nojirimycin 6-phosphate (N6P) was tested as a substrate and inhibitor for phosphoglucomutase (PGM). In the absence of glucose 1,6-bisphosphate (GBP), the incubation of PGM and N6P resulted in the complete inactivation of all enzyme activity. When equimolar amounts of N6P and GBP were incubated together with PGM, the GBP was quantitatively converted to glucose 6-phosphate (G6P) and phosphate. At higher ratios of GBP and N6P (greater than 100) the final concentration of G6P produced was found to be 19 times the initial N6P concentration. These results have been interpreted to suggest that the phosphorylated form of PGM catalyzes the phosphorylation of N6P at C-1. This intermediate rapidly eliminates phosphate to form an imine and the dephosphorylated enzyme. The dephosphorylated enzyme is rapidly rephosphorylated by GBP and forms G6P. The imine is nonenzymatically hydrated back to N6P. Occasionally (5%) the imine isomerizes to a compound that is not processed by PGM.

1-Deoxynojirimycin↗
PubMed2002

15N NMR investigation of the covalent binding of reduced TNT amines to soil humic acid, model compounds, and lignocellulose.

The five major reductive degradation products of TNT-4ADNT (4-amino-2,6-dinitrotoluene), 2ADNT (2-amino-4,6-dinitrotoluene), 2,4DANT (2,4-diamino-6-nitrotoluene), 2,6DANT (2,6-diamino-4-nitrotoluene), and TAT (2,4,6-triaminotoluene)-labeled with 15N in the amine positions, were reacted with the IHSS soil humic acid and analyzed by 15N NMR spectrometry. In the absence of catalysts, all five amines underwent nucleophilic addition reactions with quinone and other carbonyl groups in the soil humic acid to form both heterocyclic and nonheterocyclic condensation products. Imine formation via 1,2-addition of the amines to quinone groups in the soil humic acid was significant with the diamines and TAT but not the monoamines. Horseradish peroxidase (HRP) catalyzed an increase in the incorporation of all five amines into the humic acid. In the case of the diamines and TAT, HRP also shifted the binding away from heterocyclic condensation product toward imine formation. A comparison of quantitative liquid phase with solid-state CP/MAS 15N NMR indicated that the CP experiment underestimated imine and heterocyclic nitrogens in humic acid, even with contact times optimal for observation of these nitrogens. Covalent binding of the mono- and diamines to 4-methylcatechol, the HRP catalyzed condensation of 4ADNT and 2,4DANT to coniferyl alcohol, and the binding of 2,4DANT to lignocellulose with and without birnessite were also examined.

Amines↗
PubMed2005

Facile synthesis, structure, and luminescence properties of Pt(diimine)bis(arylacetylide) chromophore-donor dyads.

The luminescent complex Pt(dpphen)bis(arylacetylide) complex (1) (dpphen = 4,7-diphenylphenanthroline and arylacetylide = 4-ethynylbenzaldehyde) has been synthesized and characterized structurally and spectroscopically. Complex 1 has been employed in the synthesis of donor-chromophore (D-C) dyads through Schiff base condensations of different anilines to give imine-linked dyads 2-4 and through imine reduction with borohydride, to give the corresponding amine-linked dyads 2a-4a. Crystal structure determinations of 1-4 and 4a establish a distorted square-planar geometry around the Pt(II) ion in each system with cis arylacetylide ligands and a diimine-constrained N-Pt-N bond angle of ca. 79.5 degrees. Complex 1 is strongly emissive having a relative quantum yield (phi) of 36% and an excited-state lifetime of 3.1 micros. In accord with the notion of photoinduced electron transfer from the aniline-based donor to the photoexcited chromophore, the emission of dyads 2-4 and 2a-4a is effectively quenched in all solvents tested. The intense absorption at 400 nm (30000-70000 L/mol.cm) for 2 and 2a has been assigned as an intraligand pi-pi* transition, whereas the lowest-energy transitions for all other dyads correspond to Pt-to-pi(diimine) MLCT transitions. Although the dyads can be synthesized in a facile manner, photolysis experiments reveal that both the imine and amine linkages are photochemically unstable, resulting in hydrolysis and regeneration of the aldehyde-containing chromophore 1.

Journal Article↗
PubMed2005

Influence of ligand rigidity and ring substitution on the structural and electronic behavior of trivalent iron and gallium complexes with asymmetric tridentate ligands.

Species 1-6 are [M(III)(L)2]ClO4 complexes formed with the PhO--CH=N-CH2-Py imines, (L(I))- and (L(tBuI))-, and PhO--CH2-NH-CH2-Py amines, (L(A))- and (L(tBuA))-, in which PhO- is a phenolate ring and Py is a pyridine ring and the prefix tBu indicates the presence of tertiary butyl groups occupying the positions 4 and 6 of the phenol ring. Monometallic species with d5 high-spin iron (1, 2, 3, 4) and d10 gallium (5, 6) were synthesized and characterized to assess the influence of the ligand rigidity and the presence of tertiary butyl-substituted phenol rings on their steric, electronic, and redox behavior. Characterization by elemental analysis, mass spectrometry, IR, UV-visible, and EPR spectroscopies, and electrochemistry has been performed, and complexes [FeIII(L(tBuI))2]ClO4 (2), [FeIII(L(tBuA))2]ClO4 (4), and [Ga(III)(L(tBuI))2]ClO4 (5) have been characterized by X-ray crystallography. The crystal structures show the imine ligands meridionally coordinated to the metal centers, whereas the amine ligands are coordinate in a facial mode. Cyclic voltammetry shows that the complexes with the ligands (L(tBuI))- and (L(tBuA))- were able to generate ligand-based phenoxyl radicals, whereas unsubstituted ligands displayed ill-defined redox processes. EPR spectroscopy supports high-spin configurations for the iron complexes. UV-visible spectra are dominated by charge-transfer phenomena, and imine compounds exhibit dramatic hyperchromism when compared to equivalent amines. The tertiary butyl groups on the phenolate ring enhance this trend. Detailed B3LYP/6-31G(d)-level calculations have been used to account for the results observed.

Journal Article↗
PubMed2006

Spacially confined M2 centers (M = Fe, Co, Ni, Zn) on a sterically bulky binucleating support: synthesis, structures and ethylene oligomerization studies.

Two new bulky aryl-bridged pyridyl-imine compartmental (pro)ligands, 2,6-{(2,6-i-Pr(2)C6H3)N=C(Me)C5H3N}2C6H3Y (Y = H L1, OH L2-H), have been prepared in moderate to good overall yields via a Stille-type cross-coupling approach. The molecular structure of L2-H reveals a transoid configuration within the pyridyl-imine units with a hydrogen-bonding interaction maintaining the phenol coplanar with one of the adjacent pyridine rings. The interaction of 2 equiv of MX2 with L1 in n-BuOH at 110 degrees C gives the binuclear complexes, [(L1)M2X4] (M = Fe, X = Cl (1a); M = Co, X = Cl (1b); M = Ni, X = Br (1c); M = Zn, X = Cl (1d)), in which the metal centers adopt distorted tetrahedral geometries and occupy the two pyridyl-imine cavities in L1. In contrast, deprotonation of L2-H occurs upon reaction with 2 equiv of MX2 to afford the phenolate-bridged species [(L2)M2(mu-X)X2] (M = Fe, X = Cl (2a); M = Co, X = Cl (2b); M = Ni, X = Br (2c); M = Zn, X = Cl (2d)). 1H NMR studies of diamagnetic 1d and 2d reveal that the limited rotation of the N-aryl groups in 1d is further impeded in 2d by steric interactions imparted by the two closely located N-aryl groups. Partial displacement of the bridging bromide in 2c results upon its treatment with acetonitrile to afford [(L2)Ni2Br3(NCMe)] [2c(MeCN)]; no such reaction occurs for 2a, 2b, or 2d. Upon activation with excess methylalumoxane (MAO), 1b, 1c, 2b, and 2c show some activity for alkene oligomerization forming low molecular-weight materials with methyl-branched products predominating for the nickel systems. Single-crystal X-ray diffraction studies have been performed on L2-H, 1c, 2b, 2c, 2c(NCMe), and 2d.

Catalysis↗
PubMed1996

Occurrence of Neighboring Group Participation Reactions in Amide-N and Amidine Complexes Derived from Pentaammine(dinitrile)cobalt(III) Ions.

N-Bonded pentaamminecobalt(III) complexes of 2-cyanobenzamide, 2-cyanoacetamide, and fumaric, succinic, glutaric, and adipic amide-nitriles have been prepared. The kinetics of the base hydrolysis of (succinonitrile)pentaamminecobalt(III) have been measured: k(obsd) = k(OH) [OH(-)]; k(OH) = 1.23 x 10(3) {I = 1.00 M (NaCH(3)COO), 25 degrees C}. Amido-N-coordinated 2-cyanobenzamide cyclized in aqueous base, and it forms [(1-oxo-3-iminoisoindolino-endo-N)pentaamminecobalt(III). In aqueous acid it protonates on the exo-imine and solvolyzes (k(H) = 7.9 x 10(-)(5) s(-)(1)), forming the pentaammineaquacobalt(III) complex and 1-oxo-3-iminoisoindoline. In aqueous acid the amido-N complexes are protonated on the amide oxygen. The 2-cyanobenzamide species rearranges to form the nitrile-bonded linkage isomer in aqueous acid and also in Me(2)SO-d(6), while the succinic amide nitrile complex rearranges more slowly in aqueous acid to form solely the nitrile-bonded linkage isomer. The kinetics of the reaction were k(obsd) = f(k(H)[H(+)]/(K(a) + [H(+)])) where k(H) = 3.4 x 10(-)(4) M(-)(1) s(-)(1) and K(a) = 6.76 x 10(-)(2) M, pK(a) 1.2; pK(a) 1.3 (spectrophotometric) {I = 1.00 M (LiClO(4).3H(2)O), 25 degrees C}. In Me(2)SO-d(6) this amide-N complex reacts by three pathways: solvolysis, amide-N to -O isomerization, and amide-N to nitrile-bonded rearrangement (10%). The conjugate acid of the 2-cyanoacetamido-N complex reacted in both aqueous acid and acidified Me(2)SO-d(6) by solvolysis, amide N to O isomerization, and amide-N to nitrile-bonded rearrangement (17% in each solvent). The fumaric, glutaric, and adipic amide-nitrile complexes bonded through the amide nitrogen react only by solvolysis and amide-N to -O isomerization. Pentaamminecobalt(III) complexes of 2-cyanobenzamidine and succinic, glutaric, and adipic amidine-nitriles bonded through the amidine secondary nitrogen have been prepared. The 2-cyanobenzamidine complex undergoes rapid ligand cyclization to form the corresponding complex of 1,3-diiminoisoindoline bonded through the deprotonated endocyclic nitrogen. In aqueous acid the complex is protonated on one of the exo-imines, and this solvolyzes to form the pentaammineaquacobalt(III) complex and 1,3-diiminoisoindoline {k(H) = 1.7 x 10(-)(3) s(-)(1) (0.5 M HCl, 25 degrees C). Coordinated succinic amidine-nitrile also cyclizes in liquid ammonia to yield the complex of 2,5-diiminopyrrolidine bonded through the deprotonated endocyclic nitrogen. This is stable in aqueous base but solvolyzes rapidly (t(1/2) (s)) in aqueous acid to the aqua complex and succinimide; the latter is formed by hydrolysis of the free 2,5-diiminopyrrolidine. The dinuclear complex &mgr;-decaammine(succinonitrile)dicobalt(III) was synthesized; in aqueous base it forms &mgr;-(succinamido-N)decaamminecobalt(III). The dinuclear dinitrile complex reacts in liquid ammonia to form the corresponding succinic amidine-nitrile species which cyclizes rapidly to form &mgr;-decaammine(2,5-diiminopyrrolidino)cobalt(III) in which the ligand is bonded to cobalt(III) through the exo-imines.

Journal Article↗
PubMed2001

Hydrogen-bond mediated catalysis: the aminolysis of 6-chloropyrimidine as catalyzed by derivatives of uracil.

The aminolysis of 6-chloropyrimidine and 2-amino-6-chloropyrimidine has been examined by using density functional theory. Relative to the aminolysis of 6-chloropyrimidine, the addition of an electron-donating NH(2) group to C(2) increases the barrier to aminolysis, indicating that the third hydrogen bond does not play a catalytic role but introduces additional rigidity into the system. However, the computations suggest that there is an interesting correlation between the barrier to aminolysis and the proton affinity of the species that interacts with the incoming NH(3). To extend the range of proton affinities, the aminolysis of 6-chloropyrimidine was examined by using fluoro, imine, and thioketo derivatives of the uracil-derived bases. The proton affinity of the moiety that hydrogen bonds with NH(3) is decreased by fluoro substitution, and thus the aminolysis barriers are increased. Similarly, imine substitution enhances the PA of the moiety, which is reflected in a decrease in the aminolysis barriers. The same correlation exists for the thioketo-derived bases, whose PAs are intermediate between the fluoro and imine derivatives. Thus, the aminolysis of 6-chloropryimidine and 2-amino-6-chloropyrimidine demonstrates the importance of a well-chosen proton acceptor and the catalytic possibilities associated with the formation of multiple hydrogen bonds.

Journal Article↗
PubMed2003

Organolathanide-catalyzed regioselective intermolecular hydroamination of alkenes, alkynes, vinylarenes, di- and trivinylarenes, and methylenecyclopropanes. Scope and mechanistic comparison to intramolecular cyclohydroaminations.

Organolanthanide complexes of the type Cp'(2)LnCH(SiMe(3))(2) (Cp' = eta(5)-Me(5)C(5); Ln = La, Nd, Sm, Lu) and Me(2)SiCp' '(2)LnCH(SiMe(3))(2) (Cp' ' = eta(5)-Me(4)C(5); Ln = Nd, Sm, Lu) serve as efficient precatalysts for the regioselective intermolecular hydroamination of alkynes R'Ctbd1;CMe (R' = SiMe(3), C(6)H(5), Me), alkenes RCH=CH(2) (R = SiMe(3), CH(3)CH(2)CH(2)), butadiene, vinylarenes ArCH=CH(2) (Ar = phenyl, 4-methylbenzene, naphthyl, 4-fluorobenzene, 4-(trifluoromethyl)benzene, 4-methoxybenzene, 4-(dimethylamino)benzene, 4-(methylthio)benzene), di- and trivinylarenes, and methylenecyclopropanes with primary amines R' 'NH(2) (R' ' = n-propyl, n-butyl, isobutyl, phenyl, 4-methylphenyl, 4-(dimethylamino)phenyl) to yield the corresponding amines and imines. For R = SiMe(3), R = CH(2)=CH lanthanide-mediated intermolecular hydroamination regioselectively generates the anti-Markovnikov addition products (Me(3)SiCH(2)CH(2)NHR' ', (E)-CH(3)CH=CHCH(2)NHR' '). However, for R = CH(3)CH(2)CH(2), the Markovnikov addition product is observed (CH(3)CH(2)CH(2)CHNHR' 'CH(3)). For internal alkynes, it appears that these regioselective transformations occur under significant stereoelectronic control, and for R' = SiMe(3), rearrangement of the product enamines occurs via tautomerization to imines, followed by a 1,3-trimethylsilyl group shift to stable N-SiMe(3)-bonded CH(2)=CMeN(SiMe(3))R' ' structures. For vinylarenes, intermolecular hydroamination with n-propylamine affords the anti-Markovnikov addition product beta-phenylethylamine. In addition, hydroamination of divinylarenes provides a concise synthesis of tetrahydroisoquinoline structures via coupled intermolecular hydroamination/subsequent intramolecular cyclohydroamination sequences. Intermolecular hydroamination of methylenecyclopropane proceeds via highly regioselective exo-methylene C=C insertion into Ln-N bonds, followed by regioselective cyclopropane ring opening to afford the corresponding imine. For the Me(2)SiCp' '(2)Nd-catalyzed reaction of Me(3)SiCtbd1;CMe and H(2)NCH(2)CH(2)CH(2)CH(3), DeltaH() = 17.2 (1.1) kcal mol(-)(1) and DeltaS() = -25.9 (9.7) eu, while the reaction kinetics are zero-order in [amine] and first-order in both [catalyst] and [alkyne]. For the same substrate pair, catalytic turnover frequencies under identical conditions decrease in the order Me(2)SiCp' '(2)NdCH(SiMe(3))(2) > Me(2)SiCp' '(2)SmCH(SiMe(3))(2) > Me(2)SiCp' '(2)LuCH(SiMe(3))(2) > Cp'(2)SmCH(SiMe(3))(2), in accord with documented steric requirements for the insertion of olefinic functionalities into lanthanide-alkyl and -heteroatom sigma-bonds. Kinetic and mechanistic evidence argues that the turnover-limiting step is intermolecular C=C/Ctbd1;C bond insertion into the Ln-N bond followed by rapid protonolysis of the resulting Ln-C bond.

Journal Article↗
PubMed2004

Direct catalytic asymmetric Mannich-type reaction of hydroxyketone using a Et2Zn/linked-BINOL complex: synthesis of either anti- or syn-beta-amino alcohols.

Full details of a direct catalytic asymmetric Mannich-type reaction of a hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing the proper protective groups on imine nitrogen, either anti- or syn-beta-amino alcohol was obtained in good diastereomeric ratio, yield, and excellent enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp) imine 3 gave anti-beta-amino alcohols in anti/syn = up to >98/2, up to >99% yield, and up to >99.5% ee, while Boc-imine 4 gave syn-beta-amino alcohols in anti/syn = up to 5/95, up to >99% yield, and up to >99.5% ee. The high catalyst turnover number (TON) is also noteworthy. Catalyst loading was successfully reduced to 0.02 mol % (TON = up to 4920) for the anti-selective reaction and 0.05 mol % (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked-BINOL complex exhibited far better TON than in previous reports of catalytic asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for the high catalyst efficiency as well as transformations of Mannich adducts are also described.

Amino Alcohols↗
PubMed1981

N-hydroxyacetaminophen: a postulated toxic metabolite of acetaminophen.

The decomposition of N-hydroxyacetaminophen has been shown to occur via an initial first-order dehydration step to N-acetyl-p-benzoquinone imine with a rate constant at pH 7.6 of 8.66 x 10(-3) min-1 and a half-life of 80 min. This is followed by a complex reaction between the quinone imine and the N-hydroxy compound to ultimately yield p-nitrosophenol and acetaminophen. The glucuronide and sulfate conjugates of N-hydroxyacetaminophen have been observed as urinary metabolites of N-hydroxyacetaminophen. No N-hydroxylated metabolites were found among the metabolites of acetaminophen. These results have been interpreted to show that N-hydroxyacetaminophen is not a metabolite of acetaminophen. It is proposed that the hepatotoxicity and nephrotoxicity of acetaminophen are mediated by a direct oxidation of acetaminophen to the toxic reactive intermediate N-acetyl-p-benzoquinone imine by the cytochrome P450 dependent mixed-function oxidase system.

Acetaminophen↗