Cytotoxicity of cobalt complexes of furan oximes in murine and human tissue‐cultured cell lines

The copper complexes of 2‐furaldehyde and furan oximes have previously demonstrated potent cytotoxicity, L1210 DNA synthesis inhibition, DNA topoisomerase II inhibition and DNA fragmentation. Currently a series of cobalt metal complexes of 2‐furaldehyde oximes were compared with copper complexes of furan oximes to determine whether the type of metal is important to the cytotoxicity and mode of action of the complexes. The cobalt complexes of furan oximes, like the copper complexes, were shown to be cytotoxic to suspended tumor cell lines, e.g. leukemias, lymphomas, acute monocytic leukemia and HeLa‐S³ uterine carcinoma. The cobalt complexes did not demonstrate dramatic cytotoxicity against the growth of tumors derived from solid human tumor lines. The cobalt complexes preferentially inhibited L1210 DNA synthesis, followed by inhibition of RNA and protein synthesis from 25 to 100 µM over 60 min. These agents, like the copper complexes of 2‐furaldehyde and furan oximes, were inhibitors of DNA polymerase α activity and de novo purine synthesis with marginal inhibition of ribonucleoside reductase and dihydrofolate reductase activities with DNA fragmentation. Unlike the copper complexes, the cobalt complexes did not inhibit L1210 DNA topoisomerase II activity but did reduce thymidylate synthetase activity. Thus, varying the type of metal within the complexes of 2‐furaldehyde and furan oximes produces differences in both cytotoxicity and mode of action. Copyright © 1999 John Wiley & Sons, Ltd.     

Synthesis of azaheterocycles from aryl ketone O-acetyl oximes and internal alkynes by Cu-Rh bimetallic relay catalysts

A synthetic method for azaheterocycles from aryl ketone O-acetyl oximes and internal alkynes has been developed by using the Cu(OAc)(2)-[Cp*RhCl(2)](2) bimetallic catalytic system. The reactions proceeded with both of anti- and syn-isomers of oximes with a wide scope of substituents. The Cu-Rh bimetallic system could be applied for the synthesis of isoquinolines as well as β-carboline, furo[2.3-c]pyridine, pyrrolo[2,3-c]pyridine, and thieno[2,3-c]pyridine derivatives.     

Die heterolytische Fragmentierung von Benzoin-O-(carbamoyl)oximen

The Heterolytic Fragmentation of Benzoin-O-(carbamoyl)oximes While the known heterolytic fragmentation reactions give only three, thermal decomposition of benzoin-O-(carbamoyl)oximes results in at least four fragments: nitrile or isocyanide, carbonyl compound, CO₂ and amine. This exception is due to the transformation of the nucleofugal group 3 into the unstable carbamic acid and its decomposition (s. Scheme 1). Since only the configuration of benzoin (E)-O-(carbamoyl)oximes is satisfactory for concerted reactions, we conclude that the nitrile producing fragmentation of these (E)-compounds is concerted, whereas in the isocyanide producing fragmentation of the corresponding (Z)-compounds several steps are involved. – In contrast to the benzoin-O-(carbamoyl)oximes the pyrolysis of benzil-(E)-O-(methylcarbamoyl)oxime starts with the elimination of methyl isocyanate and the following fragmentation is that of the oxime.     

Cyclobutanones for the stereoselective synthesis of bifunctional macrolide intermediates

Beckmann fragmentation of the oximes 5 and 6 respectively, which were derived from the cyclobutanones 3 and 4, furnished the bifunctional five carbon units 7 and 8 with ca. 98% and 91% stereoselectivity.     

Mass spectra of some syn- and anti-aromatic aldoximes

The mass spectra of eight pairs of geometric isomers of aromatic oximes and four other single aromatic oximes are reported. The loss of H₂O, HO and HCN are major fragmentations from the molecular ion of all the benzaldoximes studies; however, the loss of HCN from the molecular ion did not occur in the oximes of 9-phenanthraldehyde, 1-naphthaldehyde and 2-naphthaldehyde. The halogen substituted benzaldoximes eliminate HCNO and H₂CNO forming an additional fragmentation pathway from the molecular ion. In general, variations were found for each pair of syn- and anti-oximes but no consistent patterns could be found in the spectra for all the syn-isomers versus all of the anti-isomers. The geometric isomerism of four oximes previously reported in the literature have been established for the first time as anti-m-bromobenzaldoxime, syn-9-phenanthraldoxime, syn-1-naphthaldoxime and syn-2-naphthaldoxime. Three new oxime acetates were prepared and their mass spectra are discussed.     

Investigation of the reaction between sodium hydroxide and syn-and anti-isomers of 5-substituted 2-(4-chlorobutyryl)-aminobenzophenones oximes

By the reaction of syn-isomers of 5-substituted 2-(4-chlorobutyryl)aminobenzophenones oximes with NaOH syn-isomers of 5-substituted 2-(2-oxopyrrolidin-1-yl)benzophenones oximes were obtained. Similarly the anti-isomers of 5-substituted 2-(4-chlorobutyryl)aminobenzophenones oximes treated with NaOH underwent cyclization into anti-isomers of 5-substituted 2-(2-oxopyrrolidin-1-yl)benzophenones oximes. Crystal and molecular structures were investigated of the syn-isomer of 5-methyl-2-(2-oxopyrrolidin-1-yl)benzophenone oxime, the anti-isomer of 5-bromo-2-(2-oxopyrrolidin-1-yl)benzophenone oxime, and the syn-isomer of 5-methyl-2-(4-chlorobutyryl)aminobenzo-phenone oxime. The fragmentation features under the electron impact of syn-and anti-isomers of 5-substituted 2-(2-oxopyrrolidin-1-yl)benzophenones oximes are discussed.     

Aldehyde detection by chromogenic/fluorogenic oxime bond fragmentation

Amination of 4-nitrophenol, umbelliferone and 4-methylumbelliferone gave the corresponding oxyamines 1-3. These oxyamines react with aldehydes and ketones to form oximes. In the case of aliphatic aldehydes and electron-poor aromatic aldehydes, the oximes undergo base-catalyzed fragmentation in aqueous buffer in the presence of bovine serum albumin to give the parent phenols, which is the acyclic analog of Kemp's elimination reaction of 5-nitrobenzisoxazole 28. The process can be used as a spectrophotometric assay for formaldehyde under aqueous neutral conditions.     

Mass spectra of benzoxazolone derivatives

N-Acetonylbenzoxazolones containing a substituent in the acetonyl residue, as well as their hydrazones and oximes, decompose under the influence of electron impact to give primarily fragments of N-methylene- or N-methylbenzoxazolones. For the oximes and hydrazones the characteristic ions are (M -OH) and (M — NH₂), which evidently have cyclic structures. The isomeric aryl triazinones undergo fragmentation via the scheme of the retrodiene synthesis. The characteristic ions that make it possible to distinguish the isomeric benzoxazolones, arylimidazolones, and aryltriazinones were found.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1493–1497, November, 1976.     

含磷拟除虫菊酯的研究III. 3-烷氧羰基-2, 2-二甲基环丙烷基 甲醛肟或甲基酮 肟和二烷氧基硫代磷酰氯的反应

本文研究了3-烷氧羰基-2,2-二甲基环丙烷基甲基酮肟或醛肟分别和二烷氧基硫代磷酰氯的反应,鉴定了它们的不同产物。结果表明,酮肟与磷酰氯缩合得硫代磷酸肟酯;醛肟与磷酰氯反应生成3-氰基环丙烷羧酸酯和相应的二烷基硫代磷酸,可能是经生成9再Beckmann裂解的机理。文中对上述结果进行了讨论。     

Ionisation potentials in structure analysis of isomeric nitrones,oxaziranes, O-ether oximes and acid amides

Comparative studies of the ionisation potentials and the mass spectra of some isomeric nitrones, oxaziranes, O-ether oximes and acid amides gave no evidence for hermally-induced isomerisation in the mass spectrometer. Characteristic differences in the electron-impact-induced fragmentation patterns are discussed.     

Mass Spectra of Furfuryl Aldoximes and Ketoximes

The mass spectra of 8 furfuryl aldoximes and ketoximes were studied under EI and CI conditions. Complicated fragmentation patterns were obtained in EI conditions, including formation of a furfuryl cation radical, furfuryl cation, and [M-17]⁺. The relatively simple patterns of cleavage resulted in few major ion peaks contributed from the adducts, protonation products, and dehydration products under CH₄-CI and NH₃-CI conditions. Comparison with the spectra of their isomeric amides indicated no evidence that the isomerization took place from oximes before fragmentation in both ionization methods.     

Eleuthesides and their analogs: III. Reaction of Red-Al with γ,δ-epoxy nitriles

Oxiranyl-substituted cycloalkenecarbonitriles obtained by the Beckmann fragmentation of oximes derived from levoglucosenone adducts with 1,3-butadiene, isoprene, cyclohexadiene, and cyclopentadiene were subjected to Red-Al reduction with opening of the epoxide ring. The reactions with 1,3-butadiene, isoprene, and cyclohexadiene derivatives were accompanied by cyclopropane ring closure and reduction of the cyano group to aldehyde, whereas the cyclopentadiene derivative underwent hydrogenolysis of the oxirane fragment.     

Charge-remote fragmentation and the two-step elimination of alkanols from fast atom bombardment-desorbed (M + H)+, (M + Cat)+, and (M - H)− ions of aromatic β-hydroxyoximes

Aromatic β-hydroxyoximes undergo unusual fragmentation reactions as protonated or cationized species, as radical cations, or as (M - H)^? ions, As protonated species, they expel OH ’ from the oxime functionality in violation of the even electron rule. Parallel eliminations of alkyl radicals follow OH’ loss when the aromatic ring is substituted with an alkyl chain. Alkyl radical losses appear to be characteristic of radical cations that can isomerize to ions in which the alkyl chain bears a radical site and the charged site is the conjugate acid of a basic functionality (e.g., oxime or imine). Evidence for the mechanisms was found in the ion chemistry of oxime and imine radical cations. The imine reference compounds were conveniently generated by fast atom bombardment-induced reduction of oximes, removing the requirement for using conventional chemical synthesis. Protonated imines and the (M - H)^? ions of oximes fragment extensively via charge-remote processes to eliminate the elements of alkanes. This chemistry is not shared by the protonated oximes.     

Etude de la fragmentation de semi-carbazones terpeniques

Terpene semicarbazones have been investigated using high resolution mass spectrometry. We have studied correlations between rings and functional semicarbazone degradations. The mass spectra are more complicated than the mass spectra of oximes, methyloximes and hydrazones. Cleavages are explained by known mechanisms. An interpretation of almost all the peaks is offered. The fragmentation of the semicarbazone skeleton is less marked than in the oximes. Fragmentation processes induced by the functional group are numerous. Ions obtained are concerned in secondary cleavages. Thus it is not surprising that the predominant feature is localisation of charge upon the imino nitrogen atom. Other centres may, however, be responsible for the appearance of several peaks.     

Secondary ion mass spectra of quaternary pyridine aldoximes

The secondary ion mass spectra (s.i.m.s.) of the most widely used therapeutic monoquaternary pyridine aldoximes and diquaternary pyridine aldoximes, as well as some related monoquaternary ammonium salts and neutral oximes, are reported. The monoquaternary derivatives of the oximes yield prominent intact cations which provide molecular weights, and fragmentation patterns which are dominated by even-electron ions. The diquaternary oximes investigated do not give dications, but rather undergo charge separation reactions sometimes accompanied by intramolecular aromatic substitution, and they sometimes yield monoquaternaries by expulsion of a proton. The s.i. mass spectra are structure-specific for the monoquaternary salts, allowing isomer distinction in the cases examined. Quaternary salts can be quantified by s.i.m.s., and low detection limits (less than 50 ng) are demonstrated here for the oxime salts; thus s.i.m.s. is an appropriate analytical technique for the title compounds. Procedures of derivatization which convert the neutral amines to ionic compounds, such as quaternization with alkyl halides, provide a simple means of obtaining high-quality s.i.m.s.     

Steroids and Sex Hormons. Part 263. [1]. On the Mechanism of the Reaction of 17-Hydroxyimino-steroids with Carbodiimide/Dimethylsulfoxide

Treatment of the (Z)-isomers 6 and 7 of the four isomeric 16-acetoxy-17-hydroxyimino-steroids 6–9 with DCC/DMSO/CF₃COOH (Moffat fragmentation of oximes) yielded the seco-α-acetoxy-nitriles 10 and 11 , respectively, while similar treatment of both (E)-isomers 8 and 9 gave the formyl-carbonitrile 14. The mechanism of these fragmentations is discussed. ¹³C-NMR. data of oximes are presented which show the γ-gauche effect being associated with σ (C? H)-bond polarization.     

Mass spectral characteristics of the sulfur-containing ketoxime carbamates thiofanox and metabolites

Deuterium labeling and high resolution mass spectroscopy have been used to determine the modes of electron impact fragmentation of 3,3-dimethyl-1-methylthio-2-butanone O-[(methylamino)carbonyl]oxime, thiofanox and its metabolites, the sulfoxide and sulfone. The mass spectra of the corresponding oximes were also examined. The carbamates fragmented chiefly by two competing pathways—the loss of CH₃N?C? O or the sulfur-containing moiety. The favored process was dependent on the oxidation state at sulfur. Several unusual rearrangements were noted.     

Spectrographie de masse en série du bornane I: Bornanes monosubstitués

A study has been made of the fragmentation of 2- and 3-monosubstituted bornanes. Ketones, oximes, alcohols, amines and their N-methyl derivatives were examined. Different fragmentations were compared according to the 2- or 3-position of the substituents. The results show the importance of cleavage α to the substituent bearing the charge. The α bond cleaved is that bond directed to the carbon atom with the greater degree of substitution. These results allow one to differentiate, by mass spectroscopy, the 2- and the 3-positions in the bornane skeleton.     

Pressure independence of stereomutation and fragmentation in the bis-spirocyclobutanes, anti- and syn-2,9-dicyanodispiro[5.0.5.2]tetradeca-1,8-dienes

Pressure dependent rate constants and volumes of activation for stereomutational interconversions of the cyclobutanes, anti- and syn-2,9-dicyanodispiro[5.0.5.2]tetradeca-1,8-dienes (anti-6 and syn-6), and for their fragmentation to 1-cyano-3-methylenecyclohexene (5) have been determined. Although fragmentations might have been expected to have larger and thus more positive volumes of activation than stereomutation, both processes have essentially identical volumes of activation within experimental uncertainties at 50.1 degrees C over the pressure range, 1-3000 bar: DeltaV(not equal) = (+7.4 to +9.9) +/- 2.0 cm3 mol(-1). While these positive values are consistent with the rate of entry into the hypothetical caldera being determined by breaking the weakest bond in the cyclobutanes, the insensitivity of the product-determining exit channels argues against the obligatory second bond-breaking being a significant factor in fragmentation.     

Direct Synthesis of Structurally Divergent Indole Alkaloids from Simple Chemicals

A direct and structurally divergent synthesis of indole alkaloids from very simple 2‐vinylanilines, alkynes and TBN via a novel substrate fragmentation/cycloaddition strategy has been developed, which provides an efficient noble‐metal‐free approach to access a library of highly valuable indole derivatives of tryptamines and tryptamine‐related oximes, lactams, and lactones, as well as β‐carbolines, spiroindolines, and hexa‐hydropyrrolo[2,3‐b]indoles.