Showing papers on "Hydrazone published in 2003"

Generation of phosphoranes derived from phosphites. A new class of phosphorus ylides leading to high E selectivity with semi-stabilizing groups in Wittig olefinations.

Abstract: Tosylhydrazones derived from aryl aldehydes react with t-BuOK, ClFeTPP, (MeO)3P, and aldehydes to furnish olefins with high E selectivity. These reactions occur through a Wittig-type pathway via the corresponding diazo compounds, metal carbenes and phosphorous ylides, with the water-soluble trimethyl phosphate as the byproduct. Similar reactions can also be performed using ethyl diazoacetate; however, high E selectivity was only observed in the presence of LiBr. In this case, the reaction is believed to occur via the phosphonate anion, formed through an Arbuzov reaction. Thus this olefination reaction occurs through a Horner−Wadsworth−Emmons (HWE) reaction but the phosphonate anion is generated under completely base-free conditions.

Cytotoxic iron chelators: characterization of the structure, solution chemistry and redox activity of ligands and iron complexes of the di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues

Abstract: Di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and a range of its analogues comprise a series of monobasic acids that are capable of binding iron (Fe) as tridentate (N,N,O) ligands. Recently, we have shown that these chelators are highly cytotoxic, but show selective activity against cancer cells. Particularly interesting was the fact that cytotoxicity of the HPKIH analogues is maintained even after complexation with Fe. To understand the potent anti-tumor activity of these compounds, we have fully characterized their chemical properties. This included examination of the solution chemistry and X-ray crystal structures of both the ligands and Fe complexes from this class and the ability of these complexes to mediate redox reactions. Potentiometric titrations demonstrated that all chelators are present predominantly in their charge-neutral form at physiological pH (7.4), allowing access across biological membranes. Keto–enol tautomerism of the ligands was identified, with the tautomers exhibiting distinctly different protonation constants. Interestingly, the chelators form low-spin (diamagnetic) divalent Fe complexes in solution. The chelators form distorted octahedral complexes with FeII, with two tridentate ligands arranged in a meridional fashion. Electrochemistry of the Fe complexes in both aqueous and non-aqueous solutions revealed that the complexes are oxidized to their ferric form at relatively high potentials, but this oxidation is coupled to a rapid reaction with water to form a hydrated (carbinolamine) derivative, leading to irreversible electrochemistry. The Fe complexes of the HPKIH analogues caused marked DNA degradation in the presence of hydrogen peroxide. This observation confirms that Fe complexes from the HPKIH series mediate Fenton chemistry and do not repel DNA. Collectively, studies on the solution chemistry and structure of these HPKIH analogues indicate that they can bind cellular Fe and enhance its redox activity, resulting in oxidative damage to vital biomolecules.

Synthesis of Some New Chiral Tricyclic and Macrocyclic Pyridine Derivatives as Antimicrobial Agents

Abstract: A series of chiral macrocyclic pyridines has been prepared starting from N 2 ,N 2 -(pyridine-2,6-dicarbonyl)diamino acid hydrazides (2a-c) and N,N-bis-(1-carboxy-2-substituted)-2,6-diaminocarbonyl)pyridines (3a,b). The coupling of (2a-c) with 2,6-pyridine dicarbonyldichloride (4) gave the compounds (5a-c). Compounds 2a-c were coupled with 2,6-diacetylpyridine (6) to yield compounds (7a-c) and with heterocyclic aldehydes (8) or (10) to give the compounds (9a-c) or (11a-c). In addition, the hydrazides (2a-c) were reacted with diformylcalix[4]arene 12 to afford the macrocyclic calix[4]arene hydrazone derivatives (13a-c) in reasonable yields. Finally, reaction of diaminocalix-[4]arene derivatives (14a,b) with hydrazides 2a,b or acids (3a,b), using azide or mixed anhydride methods afforded macrocyclic calix[4]arene derivatives 15a,b and 16a,b, respectively. The structure assignments of the new compounds are based on chemical and spectroscopic evidence. The biological activity screening tests showed that many of the obtained compounds exhibit high antimicrobial activity comparable to ampicillin and chloramphenicol which are used as reference compounds.

Tandem carbon-carbon bond-forming radical addition-cyclization reaction of oxime ether and hydrazone.

Abstract: The novel tandem radical addition-cyclization of oxime ethers and hydrazones intramolecularly connected with the α,β-unsaturated carbonyl group is described. The radical reaction of oxime ethers 1, 2, and 4 connected with acryloyl and methacryloyl moieties proceeded smoothly to give the heterocycles via a tandem C−C bond-forming process. The tandem reaction of hydrazone 5 took place in the presence of Zn(OTf)2 as a Lewis acid to give the trans-cyclic product 17 without the formation of the cis-isomer. The diastereoselective radical addition-cyclization reaction of chiral oxime ether 19 was also studied. The tandem reaction of 19 proceeded smoothly even in aqueous media, providing the novel method for asymmetric synthesis of γ-butyrolactones and β-amino acid derivatives.

Use of S‐pentafluorophenyl tris(2,4,6‐trimethoxyphenyl)phosphonium acetate bromide and (4‐hydrazino‐4‐oxobutyl) [tris(2,4,6‐trimethoxyphenyl)phosphonium bromide for the derivatization of alcohols, aldehydes and ketones for detection by liquid chromatography/electrospray mass spectrometry

Abstract: The synthesis of S-pentafluorophenyl tris(2,4,6-trimethoxyphenyl)phosphonium acetate bromide (TMPP-AcPFP) and the novel compound (4-hydrazino-4-oxobutyl) [tris(2,4,6-trimethoxyphenyl)phosphonium bromide (TMPP-PrG) is described and the use of these compounds as derivatizing reagents for alcohols, aldehydes and ketones evaluated. Methods have been developed for the pre-column derivatization of alcohols using TMPP-AcPFP and for aldehydes and ketones using TMPP-PrG. The reactions were investigated by the use of a variety of individual test compounds containing the target functional groups. The TMPP acetyl ester and TMPP propyl hydrazone derivatives formed with their respective target analytes produced an enhanced response in electrospray ionization mass spectrometry (ESI-MS), and reproducible chromatography. The use of these two reagents to derivatize and facilitate detection of alcohols (including sugars and steroids), aldehydes and ketones (including steroids) by LC/ESI-MS was investigated.

Phosphine-Free Suzuki-Miyaura Reactions Catalyzed by Bishydrazone-Pd-Complex

Abstract: Glyoxal bis(methylphenylhydrazone) 1 was prepared and examined as a ligand for the Suzuki-Miyaura cross-coupling reaction of aryl bromides and arylboronic acids. We found phosphine-free catalyst, such as Pd(OAC) 2 /hydrazone ligand 1 to be an efficient catalyst for a variety of substrates to produce the coupling products in good yields at room temperature.

Twisted amide reduction under Wolff-Kishner conditions: synthesis of a benzo-1-aza-adamantane derivative.

Abstract: A synthesis of 4,5-benzo-1-aza-tricyclo[4.3.1.13,8]undecane (1), a benzo-1-aza-adamantane derivative, is described and features a previously unknown application of the Wolff−Kishner reduction of a nonresonance stabilized or “twisted” amide. An intermediate amino ester is converted to a severely “twisted amide”, which, when exposed to hydrazine in alcohol, provides the corresponding “twisted” amino hydrazone. Wolff−Kishner conditions (KOH/ethylene glycol, 200 °C) provide the reduced target 1 without hydrolysis to amino acid derivatives. These operations are conveniently performed in a single flask in high yield.

Synthesis of Some New (Nα-Dipicolinoyl)-bis-L-leucyl-DL-norvalyl Linear tetra and Cyclic octa Bridged Peptides as New Antiinflammatory Agents

Abstract: In continuation to our search for new amino acid and peptide based anti-inflammatory agents, the suggestion, synthesis, structure elucidation of some N α -bis-dipicolinoyl amino acids, linear tetra and cyclic octa bridged peptides 1-9, of which four are new compounds 6-9, were herein realized. Accordingly, N α -bis-dipicolinoyl-L-leucine methyl ester 1, the corresponding acid 2, its bis-DL-norvalyl methyl ester homologue 3, the acid 4 and hydrazide 5 analogues were conventionally prepared. The tetrachlorophthalic acid hydrazine conjugate 6, anisaldehyde hydrazone 7, the benzenetetracarboxylic acid and naphthalenetetracarboxylic acid bis-L-leucyl-DL-norvalyl cyclic octa bridged peptides 8 and 9 respectively, were newly synthesized via condensation of the hydrazide 5 with the corresponding aldehyde or anhydride. The chromatographic, IR, NMR and mass spectral analysis confirmed the identities of the synthesized compounds. Comparable to the two reference antiinflammatory drugs indomethacin® and voltaren® (100%), the determined antiinflammatory potency of the candidates (carrageenan® induced paw edema in rats) revealed a general significant activity (66-94%), except for the practically inactive 6 (∼1.5 % activity). In particular, the potency of the (N α -dipicolinoyl)-bis-L-leucyl-DL-norvalyl anisaldehyde hydrazone 7 was of 94 and 87%, comparable to the reference drugs. However, 7 also showed 58% protection against ulcer formation, comparable to null for indomethacin®. Additionally, an acceptable acute toxicity was observed (LD 5 0 : 2833 mg/kg, comparable to 2700 and 2850 for indomethacin® and voltaren® respectively).

Zinc-mediated radical reaction of glyoxylic oxime ether and hydrazone in aqueous media: asymmetric synthesis of α-amino acids

Abstract: Alkyl radical addition to glyoxylic oxime ether and hydrazone in aqueous media was studied using zinc dust as a radical initiator. The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities, which could be converted into enantiomerically pure α-amino acids.

Ethylene oligomerization by hydrazone Ni(II) complexes/MAO

Abstract: The ethylene oligomerization was investigated by using new hydrazone nickel complexes Ni(N∧O)2Cl2 (2a, N^O=4,5-diazafluorene-9-one-benzoylhydrazone; 2b, N^O=4,5-diazafluorene-9-one-4-nitrobenzoylhydrazone; 2c, N^O=4,5-diazafluorene-9-one-3-nitrobenzoylhydrazone) with methylaluminoxane (MAO) in toluene. Those catalytic systems mainly assisted the dimerization of ethylene with good catalytic activity (105 to 104 g mol−1 h−1) at ambient pressure. The reaction conditions, such as the ratios of Al/Ni, reaction temperature and reaction time, were investigated. The best catalytic activity for the three complexes was observed for complex 2a without nitro-substituent on its aryl ring.

Identification of formylglycine in sulfatases by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Abstract: C(alpha)-Formylglycine, the catalytic amino acid residue in the active site of sulfatases, is generated by post-translational modification of a cysteine or serine residue. We describe a highly sensitive procedure for the detection of C(alpha)-formylglycine-containing peptides in tryptic digests of sulfatase proteins. The protocol is based on the formation of hydrazone derivatives of C(alpha)-formylglycine-containing peptides when using dinitrophenylhydrazine as a matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The hydrazone derivatives desorb and ionize with high efficiency and can be detected in the sub-femtomole range. The presence of C(alpha)-formylglycine is indicated by a mass increment of 180.13 u, corresponding to the hydrazone moiety, and also by a unique C-terminal fragment ion, characteristic of sulfatases, that becomes prominent in MALDI post-source decay mass spectra of the hydrazone derivatives.

Expeditious synthesis of new 1,2,3-thiadiazoles and 1,2,3-selenadiazoles from 1,2-diaza-1,3-butadienes via Hurd-Mori-type reactions.

Abstract: α-Substituted hydrazones obtained from 1,2-diaza-1,3-butadienes and methylenic or methinic activated substrates gave rise to a wide range of cyclic compounds. In particular, in the presence of thionyl chloride as solvent-reagent, they were transformed into 1,2,3-thiadiazoles,1 with selenium oxychloride in new 4-substituted 2,3-dihydro-1,2,3-selenadiazoles, while with selenium dioxide, they were transformed into 4-substituted 1,2,3-selenadiazoles. We have also examined the nucleophilic behavior of 1,2,3-thiadiazole 4a in the reaction with 1,2-diaza-1,3-butadienes that produced, under basic conditions, 4-hydrazono-1-(1,2,3-thiadiazolyl)pentane derivatives. This event represents an interesting example of stereoselective synthesis because it leads exclusively to the formation of the RR/SS racemic mixture. These latter compounds, treated with thionyl chloride, gave the corresponding 1,3-di-1,2,3-thiadiazolylpropane derivatives, while with sodium methoxide they afforded 1,2,3-thiadiazolyl-2-oxo-2,3-dihydro-1H-p...

A New Reaction Manifold for the Barton Radical Intermediates: Synthesis of N-Heterocyclic Furanosides and Pyranosides via the Formation of the C1−C2 Bond

Abstract: The first radical intermediate in the thiourethane-mediated deoxygenation of an alcohol (Barton−McCombie reaction) can participate in an exo-hex-5-enyl- or exo-hept-6-enyl-type radical cyclization when a suitable radical acceptor (e.g., α,β-unsaturated ester, oxime ether, or hydrazone) is appropriately placed. Carbohydrate-derived imidazolyl and triazolyl thiourethanes with such acceptors, upon addition to excess of a good hydride donor (reverse addition), undergo efficient cyclization reactions to give N-heterocyclic furanosides, and, surprisingly even N-pyranosides. Depending on the acceptor, glycosides with either a C2-amino or a C2-carbon substituent are formed.