Novel enantioselective synthesis of trans-α-(2-carboxycycloprop-1-yl)glycines: conformationally constrained l-glutamate analogues

d- and l-α-(2-carboxycycloprop-1-yl)glycines were synthesized from trans-1,3-di(2-furyl)propenone. Conversion of the double bond to a cyclopropane is followed by the formation of an oxime ether. Enantioselective reduction of the oxime ether, separation of diastereomers and oxidation of the furane rings gave enantiomerically pure d- and l-CCG I and CCG II. The structure of oxime 7b was determined by X-ray crystal structure analysis. The key step is the oxazaborolidine catalyzed enantioselective conversion of oxime ethers to amines.     

Three-step synthesis of chiral and sterically hindered amino alcohols based on cyclic enol phosphates

The new synthesis of chiral and sterically hindered 1,2-amino alcohols derivatives of 2-methyl-indane and 1,2,3,4-tethrahydrophenanthrene based on cyclic enol phosphates were investigated. The desired products were obtained using three step procedure: oxidation of accessible enol phosphates, transformation α-hydroxy ketones into corresponding oximes and finally reduction of the last one to 1,2-amino alcohols. The optimal conditions of all stages to obtain products with high enantioselectivity or diastereomeric ratio were found and elaborated. The structures and absolute configurations of (3R)-2,3-dihydro-3-hydroxy-1H-phenanthren-4-one and corresponding oxime were confirmed by X-ray analysis.     

An efficient method for selective oxidation of (oxime)Pt(II) to (oxime)Pt(IV) species using <Emphasis Type="Italic">N,N</Emphasis>-dichlorotosylamide

The oxidation of (oxime)Pt^II species using the electrophilic chlorine-based oxidant N,N-dichlorotosylamide (4-CH₃C₆H₄SO₂NCl₂) was studied. The reactions of trans-[PtCl₂(oxime)₂] (where oxime = acetoxime, cyclopentanone oxime, or acetaldoxime) with this oxidant led to trans-[PtCl₄(oxime)₂] products. The oxidation of trans-[Pt(o-OC₆H₄CH = NOH)₂] at room temperature gave trans-[PtCl₂(o-OC₆H₄CH = NOH)₂], whereas the same reaction upon heating was accompanied by electrophilic substitution of the benzene rings.     

A polarographic study of some N-oxygenated products of N-ethyl-β-methoxy-β-(3'-trifluoromethylphenyl)-ethylamine (sk and f 40652a)

The polarographic behaviour of N-hydroxy-β-methoxy-β-(3'-trifluoromethylpbenyl)-ethylamine, N-ethyl-N-hydroxy-β-methoxy-β-(3'-trifluoromethylphenyl)ethylamine and (3-methoxy-β-(3'-trifluoromethylphenyl)acetaldoxime has been studied over the pH range 0—14. The hydroxylamines gave rise to anodic and cathodic behaviour whereas the oxime gave only a cathodic wave. The mechanism of the oxidation and reduction processes was investigated by d.c. polarography and preparative micro-coulometry. The optimum pH values for analytical purposes were 7, 8 and 4 for the two hydroxylamines and the oxime, respectively. The polarographic behaviour of a mixture of the three compounds was studied and the determination of traces of such compounds by differential pulse polarography is discussed.     

A Direct Spectrophotometric Assay for Pyruvic Oxime Hydrolase

Abstract

A sensitive spectrophotometric method, which directly measures the formation of pyruvic oxime from pyruvate and NH₂OH in the UV, is described for the detection of pyruvic oxime hydrolase activity in biochemical systems. The method was used in an attempt to detect pyruvic oxime hydrolase activity in cell-free extracts from an Alcaligenes sp. which can grow on pyruvic oxime. Although substantial pyruvic oxime + nitrite oxidative activity was detected in cells and cell-free extract of this bacterium, catalysis of pyruvic oxime formation was not observed within the error of the method (～20% of the uncatalyzed rate constant of 1.9x10^?3 s^?1 at pH 7, 22°C). The rate of pyruvic oxime oxidation by cells and cell-free extract was at least 10⁵?10⁶ times greater than the rate of its hydrolysis, thus implying that oxidation of pyruvic oxime need not require prior hydrolysis. The method would appear to be applicable to hydrolases directed toward a variety of oximes.     

Enantiomerically pure α-pinene derivatives from material of 65% enantiomeric purity. Part 2: C2-symmetric N,N′-3-(2α-hydroxy)pinane diimines and diamines

The conversion of enantiomerically enriched (ee >99%) 2α-hydroxypinan-3-one and its oxime (obtained in previously described procedures¹ from α-pinene of 65% ee) into a range of derivatives with potential application in asymmetric synthesis was attempted. C₂-Symmetrical compounds, ligands for potential catalysts, were synthesized from 2α-hydroxypinan-3-one and either aliphatic or aromatic diamines. Reduction or etherification/reduction of selected diiminodiols afforded respective diaminodiols and diaminoethers, which were further transformed into azolium salts. Reactions of dipinanediaminoethers with dichlorophenylphosphine and subsequent in situ oxidation of the products afford the respective stable phosphinediamide oxides. Four selected compounds were crystallographically studied.     

The polarography of oximes: II. 1,2-Acenaphthaquinone monoxime

Polarography of 1,2-acenaphthaquinone monoxime has been carried out in buffers (pH 3.5–13.0) of constant ionic strength 0.5 M and 40% alcohol $\text{v}\text{v}$ at 25 ± 0.5 °C. The oxime group underwent diffusion-controlled reduction (4e) over the whole pH range. The number of electrons involved in the reduction was found by coulometric method as well as by incorporating the values of diffusion coefficients, obtained by using a McBain-Dawson cell, into the Ilkovi? equation. Koutecky's method has been used to compute the kinetic parameters (αn_aand ?log K_f.h) for the reduction of the oxime group and a reduction mechanism is proposed.     

The polarography of oximes: I. 9,10-Phenanthraquinone monoxime

Polarography of 9,10-phenanthraquinone monoxime has been carried out in buffers (pH 3.50 to 13.40) of constant ionic strength 0.5 M in 40% alcoholic solutions at 35 ± 0.5 °C. The oxime group underwent diffusion-controlled reduction (4e) over the whole pH range studied. The number of electrons involved in the reduction was found coulometrically as well as by incorporating the value of the diffusion coefficient, obtained by using a McBain-Dawson cell, into the Ilkovic equation. Controlled potential electrolyses and uv spectroscopic methods were used to identify the products. Koutecky's method was used to compute the kinetic parameters (αn_aand ?log k_f,h^o) for the reduction of the oxime group and reduction mechanisms are proposed.     

Spectrometric and Voltammetric Characterization of Obidoxime in Aqueous Solutions

Obidoxime is a pharmacologically active compound used as an acetylcholinesterase reactivator. The scope of this study was to establish correlations between its acid–base and redox equilibria and its mechanism as an acetylcholinesterase reactivator. The obidoxime dicationic structure is modified by the pH of the solvating medium due to tautomeric isomerizations. The possibility of stabilizing its structure as a dicationic, monocationic, and a neutral species was studied by ultraviolet–visible spectrometry and cyclic and differential pulse voltammetry. Spectrometric and voltammetric studies were performed across a large pH interval (2.00–9.80) of the solvating medium. Absorption measurements revealed the existence of three species involved in two tautomeric equilibria implying oxime and nitroso groups. The structure bearing nitroso groups, stabilized at higher pH, is more likely to behave as a nucleophilic agent than the structure with oxime groups, explaining thus its acetylcholinesterase reactivation. The obidoxime voltammetric behavior at a glassy carbon electrode is complex. Both its oxidation and reduction are diffusion-controlled processes. Anodic signals were obtained only at pH values above 6.50 and the oxidation occurs at the anion oxime group involving two electrons and one proton. The obidoxime reduction is pH dependent only for neutral or alkaline media, giving rise to two or even four signals (for pH higher than 7.50) depending on pH. The peak at less positive potentials was always well defined.     

Synthesis of DNA conjugates by solid-phase fragment condensation via aldehyde-nucleophile coupling

Oligodeoxyribonucleotides were synthesized that contain a novel nucleoside, 2′-O-(2,3-dihydroxypropyl)cytidine. Its 2′-diol group was blocked by an allyloxycarbonyl protecting group. Selective deprotection of diol group(s) of the support-immobilized blocked oligodeoxyribonucleotide by Pd(0) followed by periodate oxidation resulted in generation of the 2′-aldehyde group(s) on solid-phase. The modified oligonucleotides were used to prepare a number of conjugates with acridine, biotin and N-modified laminin peptides by oxime, hydrazone and hydrazine formation. The method may be applicable to the synthesis of oligonucleotide-peptide conjugates.     

Efficient stereocontrolled synthesis of (S)-Fmoc-β-nitroalanine via oxidation of oxime

Stereocontrolled synthesis of (S)-Fmoc-β-nitroalanine (20) was accomplished from (R)-Fmoc-Ser(^tBu)-OH (14) in a total of six steps via an oxime. The oxime (17) was obtained from (R)-Fmoc-Ser(^tBu)-H (16), which in turn was obtained by reduction of Weinreb amide (15). Oxidation of oxime was realized with peroxytrifluoroacetic acid at a neutral pH at 0 °C. After removal of the ^tBu protecting group with 90% TFA/H₂O, the hydroxyl group was oxidized with Jones reagent to afford (S)-Fmoc-β-nitroalanine (20) in overall good yield.     

The Oxime Ethers with Heterocyclic,Alicyclic and Aromatic Moiety as Potential Anti-Cancer Agents

Chemotherapy is one of the most commonly used methods of cancer disease treatment. Due to the acquisition of drug resistance and the possibility of cancer recurrence, there is an urgent need to search for new molecules that would be more effective in destroying cancer cells. In this study, 1-(benzofuran-2-yl)ethan-1-one oxime and 26 oxime ethers containing heterocyclic, alicyclic or aromatic moiety were screened for their cytotoxicity against HeLa cancer cell line. The most promising derivatives with potential antitumor activity were 2-(cyclohexylideneaminoxy)acetic acid (18) and (E)-acetophenone O-2-morpholinoethyl oxime (22), which reduced the viability of HeLa cells below 20% of control at concentrations of 100–250 μg/mL. Some oxime ethers, namely thiazole and benzothiophene derivatives (24–27), also reduced HeLa cell viability at similar concentrations but with lower efficiency. Further cytotoxicity evaluation confirmed the specific toxicity of (E)-acetophenone O-2-morpholinoethyl oxime (22) against A-549, Caco-2, and HeLa cancer cells, with an EC50 around 7 μg/mL (30 μM). The most potent and specific compound was (E)-1-(benzothiophene-2-yl)ethanone O-4-methoxybenzyl oxime (27), which was selective for Caco-2 (with EC50 116 μg/mL) and HeLa (with EC50 28 μg/mL) cells. Considering the bioavailability parameters, the tested derivatives meet the criteria for good absorption and permeation. The presented results allow us to conclude that oxime ethers deserve more scientific attention and further research on their chemotherapeutic activity.     

Synthesis of oxime ethers under single electron oxidation induced by radical cation tris(aryl)aminium salts: O-alkylation of oximes with n-vinyl lactams

O-Alkylation of (E)- and (Z)-oxime was achieved via single electron oxidation of N-vinyl lactams by using a catalytic amount of tris(aryl)aminium salts as initiator, producing the corresponding oxime ethers in high yields under mild condition. A reaction mechanism based on electron transfer was proposed.     

Preparation of 2,3- and 2,5-dihydropyrazine 1,4-dioxides from 2-hydroxyamino-2-methylpropanal oxime and some of their properties

3-Hydroxy-2,3-dihydropyrazine 1,4-dioxide derivatives were obtained by condensation of 2-hydroxyamino-2-methylpropanal oxime with glyoxal, diacetyl, and 1,2-cyclohexanedione in water, and 3-methoxy-2,3-dihydropyrazine 1,4-dioxide was obtained by condensation with diacetyl in methanol. 2,5-Dihydropyrazine 1,4-dioxide is formed when 2-hydroxyamino-2-methylpropanal oxime is heated in a solution of acetone and dilute hydrochloridic acid. The reduction of 3-hydroxy- and 3-methoxy-2,3-dihydropyrazine 1,4-dioxides and 2,5-dihydropyrazine 1,4-dioxide leads to 1,4-dihydroxypiperazines, and the bromination of 3-methoxy-2,3-dihydropyrazine 1,4-dioxide gives 5,6-bis(bromomethyl)-3-methoxy-2,3-dihydropyrazine 1,4-dioxide. 1,4-Dihydroxy-2,5-piperazinedione was obtained by oxidation of 2,5-dihydropyrazine 1,4-dioxide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1414–1418, October, 1983.     

The effect of hydrogen reduction of α-MnO2 on formaldehyde oxidation: The roles of oxygen vacancies

A series of α-MnO₂ catalysts with various Mn valence states were treated by hydrogen reduction for different periods of time. Their catalytic capacity for formaldehyde (HCHO) oxidation was evaluated. The results indicated that hydrogen reduction dramatically improves the catalytic performance of α-MnO₂ in HCHO oxidation. The α-MnO₂ sample reduced by hydrogen for 2 h possessed superior activity and could completely oxidize 150 ppm HCHO to CO₂ and H₂O at 70 °C. Multiple characterization results illustrated that hydrogen reduction contributed to the production of more oxygen vacancies. The oxygen vacancies on the catalyst surface enhanced the adsorption, activation and mobility of O₂ molecules, and thereby enhanced HCHO catalytic oxidation. This study provides novel insight into the design of outstanding MnO_x catalysts for HCHO oxidation at low temperature.     

Metal‐Free 2,2,6,6‐Tetramethylpiperidin‐1‐yloxy Radical (TEMPO) Catalyzed Aerobic Oxidation of Hydroxylamines and Alkoxyamines to Oximes and Oxime Ethers

TEMPO‐Mediated oxidation of hydroxylamines (=hydroxyamines) and alkoxyamines to the corresponding oxime derivatives is reported (TEMPO=2,2,6,6‐tetramethylpiperidin‐1‐yloxy radical; Scheme 2). These environmentally benign oxidations proceed in good to excellent yields (Table 1). For alkoxyamines, oxidation to the corresponding oxime ethers can be performed by using dioxygen as a terminal oxidant in the presence of 5–10 mol‐% of TEMPO or 4‐substituted derivatives thereof as a catalyst (Scheme 3 and Table 2). Importantly, benzyl bromides can directly be transformed to oxime ethers via in situ alkoxyamine formation by a nucleophilic substitution followed by TEMPO‐mediated oxidation (Scheme 4 and Table 3).     

Approaches to the synthesis of some tyrosine-derived marine sponge metabolites: synthesis of verongamine and purealidin N

The oxidation of tyrosine ethyl ester (7) with Na(2)WO(4)/H(2)O(2) in ethanol, dimethyldioxirane in acetone, or methyltrioxorhenium/H(2)O(2) in EtOH gave the corresponding tyrosine oxime (8) in high yield. Controlled bromination of the aromatic ring gave the monobromo oxime (9), the dibromo oxime (10), or the spiroisoxazoline (11) depending upon reaction conditions. Synthesis of the known metabolite verongamine (15) was achieved by oxidation of O-methyl bromotyrosine methyl ester and amidation of the resulting oxime ester (14) with histamine. The mono- and di-bromotyrosine oxime derivatives (9 and 10) were further transformed into the naturally occurring nitriles (16 and 17) by base hydrolysis of the ester and acid-catalyzed decarboxylation. Wadsworth-Emmons olefination of the dibromobenzaldehyde (20b) with phosphonate (18) gave the pyruvate silylenolether (21b). Deprotection and in situ oxime formation gave the oxime ester (23b). Attempted purification of the pyruvate ester resulted in a homoaldol condensation yielding butenolide (22). Amidation of the oxime ester (23b) with histamine, followed by deprotection of the MOM ether gave the first synthesis of purealidin N (28). Oxidative spirocyclization of the phenolic oxime ester (23d) with a polymer-bound iodosyl diacetate gave the spiroisoxazoline (24) and represents a formal synthesis of aerothionin (26a), homoaerothionin (26b), and aerophobin-1 (25).     

Electrochemical and sem characterization of Ag electrodes roughened by potential sweep and potential step processes in aqueous chloride and chloride + pyridine media

The effect of solution pH and the presence of pyridine on the redox behavior of Ag electrodes in aqueous chloride media is investigated. Scanning electron microscopy is used to evaluate differences in surface morphology of Ag electrodes subjected to electrochemical oxidation and oxidation—reduction processes in 0.1 M KCl and 0.1 M KCl + 0.05 M pyridine media at pH values of 2, 7, and 12. Potential sweep and potential step methods are used to effect the electrochemical oxidation and oxidation—reduction events. Comparisons are made between the resulting surface morphologies on the submicroscopic level for Ag surfaces roughened in these two ways. The redox chemistry of the oxidation and reduction processes is interpreted in terms of the different species capable of interacting with the Ag electrode surface and Ag⁺ species generated during oxidation in each medium. Surface adsorbates proposed to be important include chloride ions and pyridine. The relative importance of these species in terms of their ability to influence the redox chemistry of the Ag electrodes is seen to be a sensitive function of solution pH.     

An asymmetric synthesis of both enantiomers of 2,2,2-trifluoro-1-furan-2-yl-ethylamine and 3,3,3-trifluoroalanine from 2,2,2-trifluoro-1-furan-2-yl-ethanone

The selective conversion of 2,2,2-trifluoro-1-furan-2-yl-ethanone into (E)- and (Z)-oximes and oxime ethers and subsequent oxazaborolidine-catalyzed enantioselective reduction using different amino alcohols furnished both enantiomers of the important chiral building block 2,2,2-trifluoro-1-furan-2-yl-ethylamine with e.e. of up to 88%. Oxidation of the furan ring afforded both enantiomers of 3,3,3-trifluoroalanine in 91–93% yields.     

AgOTf and TfOH co-catalyzed isoquinoline synthesis via redox reactions of O-alkyl oximes

Under AgOTf and Brønsted acid co-catalysis, O-alkyl o-alkynylbenzaldoxime derivatives undergo a cyclization-induced N-O cleavage to produce isoquinolines with the simultaneous oxidation of O-alkyl group. This redox-based method provides a general access to diverse isoquinoline-derived heterocycles that are simple, efficient, and tolerant of various functional groups from readily available and hydrolytically stable oxime precursors.