Synthesis of naphthyridinone derivatives as potential antimalarials

In this paper we present the synthesis of 8-(4′-amino-1′methyl-butylamino)-5-(β,β,β-trifluoroethoxy)-1,6-naphthyridine ( 4 ), 8-(4′-amino-1′methylbutylamino)-6-methyl-1,6-naphthyricline-5-one ( 5 ), two 1-alkyl-3-(4′-amino-1′-methylbutylamino)-7-methyl-1,8-naphthyridin-4-ones ( 20a ) and 20b ), 3-(1′-amino-4′-methylbutyl-amino)-l-ethyl-7-methyl-l,8-naphthyridin-4-one (20c), and 4-(4′-diethylamino-1′-methylbutylamino)-7-methyl-1,7-naphthyridin-8-one ( 28 ). The compounds were evaluated for antimalarial activity in the Plasmodium berghei screen and found to be inactive.     

MENADIONE SENSITIZED PHOTOOXIDATION OF NUCLEIC ACID and PROTEIN CONSTITUENTS. AN ESR and SPIN-TRAPPING STUDY

The menadione photosensitized reactions of nucleic acid and protein constituents were studied by ESR and spin trapping. Thymine, thymidine, cytosine, 2'-deoxycytidine,5'-dCMP, uracil and several N-acetyl amino acids and dipeptides were investigated. Photolysis at 335 nm was carried out in air-saturated or Ar saturated DMSO : H₂O (1 : 1, vol/vol) containing 10 ³ M menadione and 10^-2 M 2-methyl-2-nitrosopropane as the spin trap. The observed spin adducts were explained in terms of electron transfer from the substrate to the excited triplet state of menadione to form the radical cation of the substrate and the anion radical of menadione which was also detected by ESR.     

ESR study on photodecomposition mechanism of oxidized poly(vinyl alcohol)

Photolysis behavior of oxidized poly(vinyl alcohol) (PVA) in which carbonyl groups were introduced by oxidation with sodium hypochlorite and periodic acid was investigated by using ESR spectrometry. Increased formation of PVA radicals was observed in the sample with low degree of oxidation, which showed an emphasized formation of triplet component radical. On the other hand, the formation of radicals tended to be depressed in the highly oxidized sample, and a singlet component was dominant in the ESR spectrum. By examining infrared and ultraviolet spectra of the oxidized sample, the sample was found to contain two structures, a saturated ketone group and an α,β-unsaturated group; the latter structure was intensified with increasing degree of oxidation. Based on ESR studies of the photoirradiated acetone and mesityl oxide, the models of saturated and α,β-unsaturated ketone structures in the oxidized PVA, respectively a photodecomposition mechanism of oxidized PVA was proposed.     

A mechanistic study of photodecomposition of acenaphthylene on a dry silica surface

The photochemistry of acenaphthylene (AC) has been studied on a dry silica surface at very low coverages (less than 10% of a monolayer) under aerated conditions. Adsorption of AC onto silica surface from cyclohexane follows a Freundlich adsorption isotherm, demonstrating a range of weak interactions between AC and the surface active sites. Photolysis of AC at the solid-air interface led to the formation of photo-oxidation products formed via the addition of singlet molecular oxygen to ground-state AC, and photodimers (cis and trans). The oxidation products include 1,2-acenaphthenedione (1), 2-hydroxy-1-acenaphthenone (2), 1,8-naphthalenedicarboxaldehyde (3) and 1,8-naphthalic anhydride (4). The yield of dimers increases as the surface coverage is raised. Both the excited singlet state and the excited triplet state of AC are involved in the observed dimerization on the surface.     

EPR SPECTROSCOPY OF ETHIDIUM NITRENE AND PROFLAVINE NITRENE COORDINATED TO SELF-COMPLEMENTARY DINUCLEOTIDE MINI-DUPLEXES

Abstract— Photolysis of ethidium azide ( lb ) and proflavine azide ( 2b ) immobilized in glassy media at 77 K produces triplet EPR spectra of the corresponding triplet nitrenes lc and 2c . The resonance field positions of the nitrenes are shifted by the presence of self-complementary dinucleotides. Control experiments indicated that the interaction of lc and 2c with C_PG mini-duplexes is consistent with intercalation.     

Selective formation of triplet alkyl nitrenes from photolysis of beta-azido-propiophenone and their reactivity

Photolysis of beta-azido propiophenone derivatives, 1, with built-in sensitizer units, leads to selective formation of triplet alkyl nitrenes 2 that were detected directly with laser flash photolysis (lambdamax = 325 nm, tau = 27 ms) and ESR spectroscopy (|D/hc| = 1.64 cm-1, |E/hc| = 0.004 cm-1). Nitrenes 2 were further characterized with argon matrix isolation, isotope labeling, and molecular modeling. The triplet alkyl nitrenes are persistent intermediates that do not abstract H-atoms from the solvent but do decay by dimerizing with another triplet nitrene to form azo products, rather than reacting with an azide precursor. The azo dimer tautomerizes and rearranges to form heterocyclic compound 3. Nitrene 2a, with an n,pi* configuration as the lowest triplet excited state of the its ketone sensitizer moiety, undergoes intramolecular 1,4-H-atom abstraction to form biradical 6, which was identified by argon matrix isolation, isotope labeling, and molecular modeling. beta-Azido-p-methoxy-propiophenone, with a pi,pi* lowest excited state of its triplet sensitizer moiety, does not undergo any secondary photoreactions but selectively yields only triplet alkyl nitrene intermediates that dimerize to form 3b.     

Amine-based organic high-spin systems: Synthesis,electrochemical and spectroscopic studies of polyalkylated one-dimensional oligoaryl triamines

A polyalkylated triamine, 2,2′,4,4′-tetrabromo-4″-methyl-5,5′-bis(di(3,4-di-methylphenyl)amino)triphenylamine, was designed and successfully synthesized as a model precursor for purely organic cationic high-spin systems. Cyclic voltammetry measurement revealed that the triamine gives stable mono- and dicationic states and fairly unstable tricationic state. Novel electron transfer stopped-flow (ETSF) methods were invoked for characterizing the absorption spectra of the corresponding mono- and oligo-cationic states. The triplet state of the dication was confirmed by ESR spectroscopy.     

Heterocyclic derivatives of purines. 3. Synthesis and mass spectrometric study of imidazo[1,2-]purine

A mixture containing 65% 1-methyl-2-phenyl-5,7-dichloro- and 35% 1-methyl-2-phenyl-3,5,7-trichloroimidazo [1,2-f] purine (the percentages of the components were established by means of Chromatographic mass-spectrometric analysis) was obtained by refluxing 1,8-dimethyl-2-phenylimidazo [1,2-f]xanthine in POCl₃ in the presence of excess PCl₅. Reduction of this mixture with concentrated HCl in the presence of red phosphorus leads to 1-methyl-2-phenylimidazo[1,2-f] purine, while heating with piperidine gives a mixture consisting of 55% 1-methyl-2-phenyl-6-piperidino-8-chloroimidazo [1,2-f] purine and 45% 1-methyl-2-phenyl-3, 8-dichloro-6-piperidino-imidazo [1,2-f] purine. The IR, PMR, and mass spectra of the compounds obtained are discussed.See [1] for communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1125–1129, August, 1980.     

Introduction of Benzo[h]quinoline and 1,10-Phenanthroline Subunits by Friedländer Methodology

An improved preparation of 8-amino-7-quinolinecarbaldehyde has been developed. The methyl group of 7-methyl-8-nitroquinoline may be oxidized to an aldehyde by treatment first with dimethylformamide dimethyl acetal followed by sodium periodate. Reduction with iron provides the amino aldehyde. An analogous sequence affords 1-amino-2-naphthalenecarbaldehyde. Friedl?nder condensation of the quinoline derivative with a series of acetylaromatics provides the corresponding 2-aryl-1,10-phenanthrolines. Condensation of either amino aldehyde with 1,3-diacetylbenzene or 2,6-diacetylpyridine provides the expected Friedl?nder product. Similar chemistry is described for reactions of the amino aldehydes with 1,4-diacetylbenzene, 4,4'-diacetylbiphenyl, 1,5-diacetylanthracene, 1,2,3,4,5,6,7,8-octahydroacridine-1,8-dione, and tetracyclo[6.3.0.0.(4,11)0(5,9)]undecane-2,7-dione (TCU-2,7-dione).     

微波促进下6-氨基-4-芳基-5-氰基-3-甲基-1-苯基吡啶[2,3-c]并吡唑的合成

5-氨基-3-甲基-1-苯基吡唑与芳亚甲基丙二腈在少量乙二醇中, 经微波辐射得到6-氨基-4-芳基-5-氰基-3-甲基-1-苯基吡啶[2,3-c]并吡唑衍生物, 反应4～8 min完成, 产率为71%～90%, 产物结构通过红外、核磁共振、元素分析及单晶X射线分析表征.     

Photochemistry of kynurenine, a tryptophan metabolite: properties of the triplet state

Photolysis of aqueous kynurenine (KN) solutions results in the formation of triplet kynurenine TKN. In low pH solutions, triplet formation occurs with almost 100% efficiency, while in neutral solutions the triplet quantum yield is PhiT = 0.018 +/- 0.004. The dissociation constant of TKN, which is attributed to deprotonation of the anilino group, has a pKa value of 4.7. Similar triplet absorption spectra were obtained under direct and acetone-sensitized photolysis. The large difference in quantum yields as a function of pH is attributed to excited-state properties of the first excited singlet state of KN. The rate constant quenching for TKN by oxygen is kq = 2 x 10(9) M(-1) s(-1).     

Photo-induced radical formation in cellulose

The characteristics of cellulose radicals produced by photo-irradiation were studied from their ESR spectra. All spectra of the irradiated samples contained a singlet spectrum with a line width of 28 gauss. Spectra consisting mainly of a single absorption line were observed in the initial stage of irradiation. With the elapse of irradiation time, two absorption lines with a line width of 8 gauss were added to the original singlet spectrum, leading to the three absorption lines widths of 8, 28, and 8 gauss, respectively, of which the middle line with a line width of 28 gauss showed the maximum intensity. This three-line spectrum was easily produced when hydrogen peroxide or metallic ions such as Fe³⁺, Ag⁺, Fe²⁺, and Ce⁴⁺ were used as sensitizers. The observed ESR spectra consisted of a singlet with a line width of 28 gauss and a triplet with a line width of 8 gauss and a splitting factor of 28 gauss. The triplet component was more unstable toward warming, as compared with the singlet component. Based on the experimental results, it was suggested that cellulose radicals due to the scissions of cellulose chains corresponding to the ESR spectra with a single line could be the most important factor for the initiation of graft copolymerization.     

Pivalyl-r-butylmethylene and its quintet radical pair: Isolation and ESR detection

Pivalyl-t-butylmethylene was Generated by the photolysis of 2,2,5,5,-tetramethyl-4-diazo-3-hexanone at T < 22 K. As expected. only one set of triplet signals was observed in the ESR which was assigned to pivalyl-r- butylmethylene, the first alkyl substituted ketocarbene isolated, in the trans conformation. In addition a set of weak, but well-reproducible signals was also observed and it was assigned to the quintet state triplet radical pair. Photolysis of the analogous 3-diazo-2-butanone, however, fails to generate any triplet signal indicating that probably Wolff rearrangement with migration of a methyl and/or 1.2-H shift can compete successfully with ISC from the singlet ketocarbene.     

Synthesis of SMP-797: a new potent ACAT inhibitor

A potent ACAT (acyl-CoA: cholesterol acyltransferase) inhibitor SMP-797 was effectively synthesized by the urea formation of 3-amino-4-aryl-1,8-naphthyridin-2(1H)-one and 4-amino-2,6-diisopropylamine. The synthesis of the former compound involved the Suzuki coupling reaction as a key step, and the latter was prepared by the 4-selective nitration of 2,6-diisopropylaniline using 2,3,5,6-tetrabromo-4-methyl-4-nitro-2,5-cyclohexadienone.     

Ferromagnetic spin alignment in head-to-tail coupled oligo(1, 4-phenyleneethynylene)s and Oligo(1,4-phenylenevinylene)s bearing pendant p-phenylenediamine radical cations

The intramolecular and long-range ferromagnetic coupling between p-phenylenediamine radical cations in head-to-tail coupled oligo(1, 4-phenyleneethynylene)s and oligo(1,4-phenylenvinylene)s between neighbors and next-nearest neighbors is described. UV/vis/near-IR experiments show that the radical cations are localized in the pendant p-phenylenediamine units of the conjugated oligomers. The ESR spectra of these oligo(1,4-phenyleneethynylene) and oligo(1, 4-phenylenvinylene) di(radical cation)s are consistent with those of a triplet state. A linear behavior is observed for the doubly integrated ESR intensity of the DeltaM(s) = +/-1 and DeltaM(s) = +/-2 signals with the inverse temperature (I approximately 1/T), consistent with Curie's law. This behavior indicates a triplet ground-state diradical with a large triplet-singlet energy gap or possibly a degeneracy of singlet and triplet states.     

Photochromism of photoenolizable ketones in quinoline and 1,8-naphthyridine series studied by time-resolved absorption spectroscopy

For the two photochromic molecules, 3-benzoyl-2-benzyl-1-methyl-1H-quinolin-4-one (QC1) and 3-benzoyl-1,2-dibenzyl-1H-1,8-naphthyridin-4-one (QC18a) as well as the nonphotochromic 3-benzoyl-1-benzyl-2-methyl-1H-1,8-naphthyridin-4-one (QC18b), the full photochemical mechanism, which is based on the photoenolization process, has been elucidated using stationary and time-resolved spectroscopy techniques. After photoexcitation, the S1(n,pi*)-T1(n,pi*) ISC process involving the exocyclic carbonyl chromophore is demonstrated to occur. Subsequently, gamma-hydrogen transfer proceeds very rapidly to give rise to the triplet photoenol with a probable 1,4-biradical structure. For all three molecules, the biradical is clearly detected and proved quantitatively to be the direct precursor of the colored form (photochromic compounds) or ground state starting material (nonphotochromic compound). Solvent effects for the three molecules studied may suggest the existence of intramolecular hydrogen bonding in both biradical and colored form species. Structural effects on the gamma-hydrogen transfer rate and biradical decay are related to the photochromic performances.     

5-丁基-9-苯基-4,5,6,9-四氢苯并[d.e]噁唑[5,4-g]-异喹啉-4,6-二酮的合成

本文给出了一条较好的制备5-丁基-9-苯基-4,5,6,9-四氢苯并[d.e]吣唑[5,4-g]-异喹啉-4,6-二酮的反应路线,即:先由4-溴-1,8-萘酐经亚胺化、硝化、水解和还原等反应制得N-丁基-3-硝基-4羟基-1,8萘酰亚胺,再在硼酸的存在下,将亚胺与苯甲酰氯反应可得到目标化合物。文中给出了该化合物的质谱、核磁共振、红外、紫外和荧光等光谱数据。     

Synthesis of 3-[[(2-benzimidazolyl)thio]methyl]-1-methyl-1,8-dihydrocycloheptapyrazol-8-ones

3-(Bromoacetyl)tropolone was reacted with five 2-mercaptobenzimidazoles to give 3-[[(2-benzimidazolyl)thio]acetyl]tropolones. These products were heated with methylhydrazine to afford 3-[[(2-benzimidazolyl)thio]methyl]-1-methyl-1,8-dihydrocycloheptapyrazol-8-ones. In these reactions, 1-methyl-3-[(1-methylhydrazino)methyl]-1,8-dihydrocycloheptapyrazol-8-one was isolated as a minor product.     

Photoproduction of remarkably stable benzylic radicals in cyclodextrin inclusion complexes

Photolysis of cyclodextrin inclusion complexes of diastereomers of ,′-dimethyldibenzyl ketone in the solid state resulted in stable benzylic radicals at room temperature. These radicals were characterized by their electron spin resonance (ESR) signals, emission and excitation spectra.     

Friedländer reaction of 3-acetyltropolones: Synthesis of naphthyridinyl- and allied heterocyclic-substituted tropolones

Five 3-acetyltropolones reacted with 2-amino-3-pyridinecarbaldehyde to afford the corresponding 3-(1,8-naphthyridin-2-yl)tropolones in excellent yields. In a similar manner, 1,6-naphthyridin-2-yl-,1,7-naphthyridin-2-yl-, 6-pyrido[2,3-b]pyrazinyl-, and 1-methyl-6-pyrazolo[5,4-b]pyridyl-substituted tropolones were prepared. Reactivities of amino-substituted heteroarenecarbaldehydes in these reactions and properties of the products are also discussed.