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The biologically relevant alkylations of the thiolate ligands in tripod zinc thiolates by methyl iodide were studied kinetically. This was undertaken to elucidate the factors that affect the rate of alkylation by varying the donor sets of the tripods, the nature of thiolates, and the steric requirements of tripod.

The stereochemical outcome of the alkylation of a variety of phenyglycinol-derived oxazolopiperidone lactams is studied. The synthetic utility of the alkylation reactions is illustrated with the synthesis of cis and trans 3,5-disubstituted, 2,5-disubstituted and 2,3,5-trisubstituted enantiopure piperidines and the indole alkaloids 20R- and 20S-dihydrocleavamine.

The multifunctional DNA repair enzymes apurinic/apyrimidinic (AP) endonucleases cleave DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases in the base excision repair pathway. Alternatively, in the nucleotide incision repair (NIR) pathway, the same AP endonucleases incise DNA 5' of a number of oxidatively damaged bases. At present, the physiological relevance of latter function remains unclear. Here, we report genetic dissection of AP endonuclease functions in base excision repair and NIR pathways. Three mutants of Escherichia coil endonuclease IV (Nfo), carrying amino acid substitutions H69A, H109A, and G149D have been isolated. All mutants were proficient in the AP endonuclease and 3'-repair diesterase activities but deficient in the NIR. Analysis of metal content reveals that all three mutant proteins have lost one of their intrinsic zinc atoms. Expression of the nfo mutants in a repair-deficient strain of E. coli complemented its hypersensitivity to alkylation but not to oxidative DNA damage. The differential drug sensitivity of the mutants suggests that the NIR pathway removes lethal DNA lesions generated by oxidizing agents. To address the physiological relevance of the NIR pathway in human cells, we used the fluorescence quenching mechanism of molecular beacons. We show that in living cells a major human AP endonuclease, Ape1, incises DNA containing [alpha]-anomeric 2'-deoxyadenosine, indicating that the intracellular environment supports NIR activity. Our data establish that NIR is a distinct and separable function of AP endonucleases essential for handling lethal oxidative DNA lesions. apurinic/apyrimidinic endonuclease | oxidative DNA damage | tert-butyl hydroperoxide | 3'-blocking groups | [alpha]-anomeric 2'-deoxyadenosine

Alkylation of metal carbonate in various ionic liquids with 1-bromo-3-phenylpropone as a model reactant was investigated. A new phosgene-free method for the synthesis of symmetrical organic carbonates through alkylation of metal carbonate with various alkyl halides and sulfonates in 1-n-butyl-3-methyl-imidazolium hexafluorophosphate, as an ecofriendly reaction media was reported.

The alkylation of m-cresol with isopropyl alcohol in the presence of novel superacidic catalysts named as UDCaT-4, UDCaT-5, and UDCaT-6 is investigated. UDCaT-5 is found to be the best catalyst in terms of activity and selectivity.

A study is conducted which aims to understand the chemistry of the Fe-C functionality in the bis-iminopyridine Fe catalyst. The results of the alkylation of the bis-iminopyridine-FeCl2 catalyst with R-LI are described.

The selective arene alkylation by alpha-chloronorborene catalyzed by electrophilic metallocenium ion pairs has been described. Control experiments and reactivity studies on each component step suggest a mechanism involving participation of the metal electrophiles in the catalytic cycle.

Chelated enolates react with excellent selectivities not only in palladium-catalyzed allylic alkylations but also in Michael additions is demonstrated. Chelated amino acid ester enolates are versatile nucleophiles for both reactions giving high yields and selectivities.

Highly enantioselective palladium-catalyzed asymmetric allylic alkylation using a novel chiral pyrrolidinyl-containing amino-phosphine ligands having a hydroxyl group is described. The trialkylsilylated aminophosphine ligand gave good results in the palladium-catalyzed asymmetric allylic alkylation.

A zinc enamide generated from the corresponding N-aryl imine undergoes addition to an unactivated olefin, to generate an alpha-alkylated gamma-zincioimine intermediate in good to excellent yield. The organozinc intermediate undergoes further C-C bond formation with a carbon electrophile to give, upon hydrolysis of the imine, an alpha-alkylated ketone.

The antitumor activity of S23906-1, a derivative of acronycine, is mediated by forming DNA covalent adducts at guanine-N2 in the minor groove. Data indicate that the anticancer compound interacts with both cell free DNA and genomic DNA.

Results suggest that antihydrophobic ethanol increases the solubility of hydrophobic molecules in water and the carbon alkylation involves a transition state with benzyl group packing onto the phenol ring. Further, oxygen alkylation employs the n electrons of the phenoxide oxygen as the nucleophile.

This article describes the basic radical reactivity of organoboranes toward generating carbon-centered radicals via cleavage of carbon-boron bonds. Research interests in the utilization of organoboranes as radical initiators and radical precursors are also discussed.

Research has been conducted on the (+ or -)-scopadulin, an aphidicolane diterpene. The total synthesis of (+ or -)-scopadulin accomplished by the chemo- and stereoselective methylation is discussed.

Density-functional theory and coupled-cluster singles and doubles theory with perturbative corrections for triples excitations (CCSD(T)) electronic structure method is employed to investigate the effect of alkylation on the binding strength of oxygen and nitrogen donors to silver (I). Results based on the structural study and incremental binding enthalpies of Ag(super +)(L)n ionic clusters depicted initial increase as a function of the degree of alkylation.

Research has been conducted on several primary amines. The alkylation of these amines with crotyl bromide followed by acylation with methyl malonyl chloride that induced radical cyclization is discussed.

Research has been conducted on the NaBH(OAc) (sub)3. Results indicate that this compound is a preferred reagent over NaBH (sub)3 CN for the N-alkylation of amino acid esters by reductive amination.

Research has been conducted on the N-benzyl-N-chloroacetyl amino acid derivatives. The base-assisted intramolecular alkylation of these derivatives has been conducted and the results of the experiment are presented.

Research has been conducted on the (eta (super)5 -cyclopentadienyl)dicarbonyliron carbene complexes. The generation of these complexes from thioether derivatives by S-alkylation with thrimethyloxonium tetrafluoroborate and loss of thioanisole has been investigated.

Research has been conducted on the ion structure of R (sub)2 N[N(O)NO] (super)- and their alkylation products. Results indicate that these diazeniumdiolate anions can displace halide from electrophilic aza- and nitroaromatic substrates to form O (super)2 -arylated derivatives of R (sub)2 N-N(O)=N-OAr.

Research has been conducted on the trisubstituted oxiranes. The synthesis of these oxiranes based on the deprotonation-alkylation of the stereodefined simpler oxazolinyloxiranes has been carried out and the results are discussed.

Petroporphyrin compositional analysis of a heavy crude oil has been realized by isolation and subsequent ESI--FT-ICR mass spectrometric analysis of the porphyrin-containing fractions. Vanadium octaethyl (V=O(II)OEP) and nickel octaethyl (Ni(II)OEP) porphyrin standards were analyzed to determine favorable electrospray ionization conditions and provide insight as to the molecular species present (e.g., adducts, multimers). Standard V=O(II)OEP and Ni(II)OEP solutions revealed the presence of both monomer and dimer species with a greater relative abundance of monomers. In contrast, mass spectral analysis of a porphyrin fraction from Cerro Negro crude oil was dominated by dimeric species. M[S.sup.3] analysis identified a dioctylphthalate (DOP) contaminant, likely introduced during fractionation of the crude oil. DOP-porphyrin complexes and porphyrin-porphyrin dimers were then identified. Infrared multiphoton dissociation (IRMPD) of dimeric species produced the corresponding monomers with minimal fragmentation. The monomeric petroporphyrins were analyzed to reveal the metal (Ni(II) or V=O(II)), porphyrin type (e.g., etio vs. DPEP), and distribution of alkylation. Key words: petroporphyrin, porphyrin, petroleum, electrospray ionization, mass spectrometry, Fourier transform, ion cyclotron resonance, ICR, FT-ICR, FTMS.

Research has been conducted on the acylation reaction regioselectivity. The results indicate that regioselectivity of the Vilsmeier-Haack reaction can be explained by the stability of the cationic intermediate resulting from the attack on C (sub)4.

Research has been conducted on the tertiary amines. The preparation of these amines via secondary amine N-alkylation treated with alkylating agents and search for the reagents useful for the parallel synthesis are discussed.

Research has been conducted on the Birch reduction-alkylation of substituted benzamides from L-prolinol. The preparation and the Birch reductive alkylation of 3-substituted 2-methyl-2,3-dihydroisoindol-1-ones has been carried out and the results are presented.

The behavior of the ion-pair of the alkylation of sodium 4-nitrophenoxide by iodomethane in acetone-water mixtures is dependent on the solvent medium, the dielectric constant of which influences the electrostatic interactions of the reaction. Further, the solute-solvent interactions also play a role in the alkylation reaction.

Research describes the synthesis of norbornane-based chiral ligand phosphinooxathiane and pulegone-based phosphinooxathiane with their usage in the asymmetric palladium-catalyzed allulic substitution reactions and allylic acetate alkylation and amination.

Michael alkylation of cyclohexanone benzylimines with ethylidenemalonate diesters exhibits an inverse regioselectivity, while with imines the stereochemistry of the diastereomeric Michael adduct exhibits a chairlike complex with exo position for the beta-methyl group of the ethylidenemalonic acid diesters.

Research describes the Michael addition of o-Quinone methide to amines, sulfides, amino acids, and glutathione to obtain alkylated adducts. The reactivity of quinone methides toward nitrogen and sulfur nucleophiles spreads over 7 order of magnitude from water to 2-mercaptoethanol.

Results show that naphthalene group of azinomycin binds to DNA by intercalation as revealed by fluorescence spectroscopy, DNA winding, viscometry, and equilibrium dialysis analyses. Mechanism of the cytotoxicity of azinomycin is discussed.

Research describes the preparation of a series of novel phosphine-phosphite ligands containing a chiral phosphine moiety, which serve as ligands in the palladium catalyzed allylic alkylation reactions. The reaction of diphenyl-2-propenyl acetate with dimethyl malonate, mediated by these ligands exhibits good enantioselectivities.

This review discusses the rate and selectivity of metal-catalyzed reactions as influenced by the bite angle of the bidentate ligands. Data reveal that ligands are involved in the stabilization or destabilization of the reaction intermediates and the bite angle brings about the steric hindrance between the ligand and the substrate.

Research has been conducted on the mitosene antitumor agents. The reductive alkylation chemistry of these agents has been investigated.

Research explores the synthesis of cyclodextrin derivatives containing the same substituent for the hydroxyl groups at the 2-, 3-, and 6-position. Data discuss the electrophilic reaction mediating the production of the monoalkylated cyclodextrin derivatives.

Results show that by nucleophilic substitution of the allylic bromine in 2-bromomethyl-7-4'-dimethoxyisoflavone using either ethyl cyanoacetate, or cyanide anions, or palladium-catalyzed ethoxycarbonylation, bridged bis-isoflavones can be prepared. Data indicate that a double alkylation reaction leads to the formation of bis-isoflavones.

Research has been conducted on N,N-dimethylformamide (DMF). The rate of the DMF exchange in the nickel(II) cation and in the monochloro species has been investigated via (super)13 C NMR spectroscopy.

Results indicate that the stability of phosphodiester-quinone methide adduct, trialkylphosphate, is increased by lowering the resonance capacity of the p-hydroxy substituent. Alkylation of a phosphodiester via p-quinone methide and in situ lactonization by a catechol derivative are described.

A synthetic route to P-chirogenic trialkylphosphine-boranes involves an optically active secondary dialkylphosphine-borane as an intemediate. Research shows that the methodology is applicable for the synthesis of analogous phosphine-boranes and phosphine ligands.

The present study reports a procedure developed for the identification of SDS-polyacrylamide gel electrophoretically separated proteins using an electrospray ionization quadrupole time-of-flight mass spectrometer (Q-TOF MS) equipped with pressurized sample introduction. It is based on in-gel digestion of the proteins without previous reduction/alkylation and on the capability of the Q-TOF MS to provide data suitable for peptide mass fingerprinting database searches and for tandem mass spectrometry (MS/MS) database searches (sequence tags). Omitting the reduction/alkylation step reduces sample contamination and sample loss, resulting in increased sensitivity. Omitting this step can leave disulfide-connected peptides in the analyte that can lead to misleading or ambiguous results from the peptide mass fingerprinting database search. This uncertainty, however, is overcome by MS/ MS analysis of the peptides. Furthermore, the two complementary MS approaches increase the accuracy of the assignment of the unknown protein. This procedure is thus, highly sensitive, accurate, and rapid. In combination with pressurized nanospray sample introduction, it is suitable for automated sample handling. Here, we apply this approach to identify protein contaminants observed during the purification of the yeast DNA mismatch repair protein Mlh1.

Research discusses the use of the palladium-catalyzed asymmetric allylic alkylation (AAA) reaction in the synthesis of barbituric acid derivatives, cyclopentobarbital and pentobarbital, at 91% and 81% yield, respectively.

Analogue 7 of the duocarmycins and CC-1065 manifested increased solvolysis reactivity at pH 3. Theincrease, which is consistent with the increased electron-withdrawing properties and conjugation of thioamides relative to amides, can be attributed to a diminished vinylogous amide stabilization of the reacting alkylation subunit. Amidine 6, which underwent preferential N2 amidine linkage hydrolysis, was found to be more unstable than 7 despite the diminished electron-withdrawing properties.

Allylic alkylations via titanated nucleophiles with palladium as the catalyst have been studied. The allylic alkylations are used in the clean allylation of active methylene compounds with high and predictable regio-, diastereo-, and enantioselection. It has been observed that Ti(OPr-i)4 facilitates the addition of a wide range of carbon acids on allylic acetates in the presence of palladium. Ti(OPr-i)4 can be used for a wide range of nucleophile pKa window and is as efficient as enolizing systems based on BSA/AcOK.

The thiophenecarbonyl coupling reactions of 2- and 3-thiophenecarbaldehydes mediated by SmI2/hexamethylphosphoramide (HPMA) have been studied. A new method has also been developed for elaborating thiophenecarbaldehydes to furans alpha,beta-unsaturated-gamma-lactones and other thiopene-fused polycyclic compounds. The coupling reactions result in C-5 hydroxyalkylation products. The initial reaction occurred at C-2 and subsequent alkylation happened at the sulfur atom which was accompanied by the opening of the thiopene ring to accomodate gamma-lactols.

The diastereoselective alkylation of suitably protected 3-substituted tetrahydroisoquinolines has been studied. The compound is readily available in enantiomerically pure form from L-phenylalanine by converting to the pure amino alcohol via Pictet-Spengler cyclization followed by reduction with LiAlH4. The diastereoselectivity is due to the steric bias from the bulky tert-butyldimethylsilyloxy group which directs the incoming electrophile to the opposite face.

The alkylation reactions of 4 equiv of alkyl halides in the presence of 2 equiv of (Bu3Sn)2 and 4 equiv of 1,4-diazabicyclo(2.2.2)octane (DABCO) has been studied. Homolytic base-promoted alkylations with (Bu3Sn)2 and DABCO in C6H6 at 60 degrees C has been observed. The aromatic substitution may be a general process for aromatic compounds with electron-bearing substituents. The reaction complements the Friedel-Crafts reaction which can alkylate benzene derivatives with electron-donating substituents.

The allylic alkylation of allylic esters and allylic alcohols was done using an iridium complex. The iridium complex proved to be an efficient catalyst and alkylation at the substituted allylic terminus was realized using (E)-2-alkenyl esters and 1-substituted-2-propenyl esters. However, the regioselectivity was reversed when (Z)-2-alkenyl esters were used. It was also observed that (Z)-selective allylic alkylation could also be done at the unsubstituted allylic terminus.

1-(Alkylamino)-3,5-dichloro-2,4,6-trinitrobenzenes were synthesized through aromatic substitution reactions that involve sym trichlorotrinitrobenzene and amines. The yields and relative formation were found to be a function of the degree of alkylation of the nucleophile. For ammonia and monoalkylamines, the introduction of a second and third donor was supported. The findings were attributed to the intramolecular hydrogen bonding as verified by X-ray analysis of 3,5-dichloro-2,4,6-trinitroaniline.

Bivalent sialyl Lewis x derivatives and sialyl Lewis x carboxylic acids were chemoenzymatically synthesized to investigate their inhibitory activities. The products underwent assaying to test for inhibition against binding of a sLe(super a)-polymer to immobilized E- and P-selectin. For the E-selectin assay, all dimers had smaller IC50 values compared to the sLe(super x) monomer. The results further showed that comparable binding improvements can be achieved with linkers of totally different rigidity and length.

The intramolecular Diels-Alder reaction of furandiene with allenyl ethers followed by the rearrangement of sulfur and silicon atom-containing group were described. For the 5-(alkylthio)-2-furfuryl propargyl ethers, the alkylthio group 1,4-rearrangement products were exclusively derived and the alkylthio group 1,4-rearrangement occurred intramolecularly through tight ion pairs. For 5-(alkylsulfonyl)-2-furfuryl proparyl ethers and the 5-(alkylsulfinyl)-2-furfuryl proparyl ethers, alkylsulfonyl and alkylsulfinyl group 1,2-rearrangement products were derived, respectively.

Derivatives of 1,4-diacylnaphthalenes were examined to determine the relationship between the dimension of the carbonyl-bonded alkyl groups and the interconversion barriers. Structural assignment was made possible by observing the conformer ratio at equilibrium with respect to the solvent polarity. For the bulky tert-butyl derivative, both isomers were isolated at low temperature and, by using X-ray data, the solid-state assignment was transferred to solution nuclear magnetic resonance signals under nonequilibrium conditions.