RESUMO
A new method to synthesize γ-carboline derivatives has been developed starting from 3,5-dibromo-4-pyridinamine by monoarylation using the Suzuki-Miyaura cross-coupling reaction followed by the base-mediated ring closure to pyrrole formation. Synthesis of a series of γ-carboline derivations from the 4-brominated γ-carboline 4a has been achieved by employing various coupling reactions and N-alkylations. This method has been applied for the synthesis of the antimalarial and anticancer natural product isocryptolepine. The photophysical properties of novel γ-carboline derivations are also reported.
Assuntos
Carbolinas , Alcaloides Indólicos , Estrutura Molecular , QuinolinasRESUMO
Despite the availability of selective synthetic approaches to multifunctionalized substituted olefins, the cyanothiolation of internal alkynes has been much less explored. Herein, we show that nonactivated internal alkynes can be successfully cyanothiolated with diaryl disulfides and tert-butyl isocyanide in the presence of a Pd catalyst (e.g., Pd(PPh3)4) with the release of isobutene and arenethiol to afford ß-thiolated alkenyl cyanides in yields of 34-89%.
RESUMO
Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1) has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2)c cells by measuring HIF response element (HRE) promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity.
Assuntos
Furanos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Oxigenases de Função Mista/antagonistas & inibidores , Proteínas Repressoras/antagonistas & inibidores , Tiofenos/farmacologia , Domínio Catalítico/efeitos dos fármacos , Linhagem Celular , Furanos/síntese química , Furanos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Oxigenases de Função Mista/química , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteínas Repressoras/química , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Tiofenos/síntese química , Tiofenos/química , Ativação Transcricional/efeitos dos fármacosRESUMO
Binary systems consisting of benzoyl peroxide (BPO) and diorganyl diselenide are effective in the selective benzoyloxyselenation of internal alkynes to afford the corresponding ß-(benzoyloxy)alkenyl selenides in good yields. In contrast to internal alkynes, terminal alkynes undergo a novel C(sp)-H substitution with the phenylseleno group of the BPO/(PhSe)2 system, providing alkynyl selenides in good yields. Both selenation reactions might proceed via benzoyloxy selenide (PhC(O)O-SeAr) as a key intermediate for electrophilic addition to alkynes. The products alkenyl and alkynyl selenides are expected to be useful synthetic intermediates in organic synthesis.
RESUMO
Transition metal-free access to 1H-indazolones 1 has been achieved on the basis of base-mediated intramolecular C-N bond formation. Reactions of 2-halobenzohydrazides 2 with potassium tert-butoxide in the presence of catalytic proline provided indazolones 1 in moderate to good yields. This transformation may proceed primarily via the radical pathway according to the control experiment with a radical scavenger.
RESUMO
A facile and rapid access to resveratrol derivatives has been achieved based on palladium-catalyzed oxidative Heck reaction of aryl boronic acids with styrenes followed by demethylation in moderate to good yields. A series of resveratrol derivatives with various functional groups has been synthesized easily. The radioprotective activity of synthesized compounds has also been evaluated using rat thymocytes. The results revealed that some resveratrol derivatives efficiently protected the thymocytes from radiation-induced apoptosis.
Assuntos
Protetores contra Radiação/química , Estilbenos/química , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ácidos Borônicos/química , Catálise , Raios gama , Oxirredução , Paládio/química , Protetores contra Radiação/síntese química , Protetores contra Radiação/farmacologia , Ratos , Resveratrol , Estilbenos/síntese química , Estilbenos/farmacologia , Relação Estrutura-Atividade , Estirenos/química , Timócitos/efeitos dos fármacos , Timócitos/metabolismo , Timócitos/efeitos da radiaçãoRESUMO
The matrix effects (ME) in simultaneous analysis of pesticide residue using liquid chromatography-tandem mass spectrometry (LC-MS/MS) were evaluated by comparing the slopes of matrix-matched and reagent-only calibrations of four types of vegetable samples. Both the sampling and measurement variances of the ME were also determined using one-way analysis of variance. Substantial ion suppression (ME<-20%) was observed in komatsuna, spinach, and tomato when a modified Japanese official method was implemented. The ME magnitude varied significantly due to sample variability for some pesticides, but it varied by no more than 4% as a result of analytical procedure variance. This study also showed that the addition of stable isotope-labeled internal standards at low concentrations improved the recovery of pesticides from samples at various residue levels. The findings of this study highlight the importance and practical application of internal standards and the matrix-matched calibration method in residue analysis using LC-MS/MS.
RESUMO
Orobanchaceae root parasitic weeds cause significant damage to agriculture and become threats to global food security. Integrated pest management is a key concept in modern agriculture and requires chemicals with various modes of action. Planteose accumulates as a storage carbohydrate in the dry seeds of root parasitic weeds. In Orobanche minor seeds, planteose is hydrolyzed by an α-galactosidase, OmAGAL2, during germination. It was found that the OmAGAL2 inhibitor, PI-28, suppressed the radicle elongation of germinating O. minor seeds. This inhibitory activity against O. minor radicle elongation was evaluated for a series of aryloxyacetylthioureas synthesized based on the structure of PI-28. Compounds with a 3-Cl or 4-Cl substituent on the benzene ring in the phenoxy moiety in PI-28 exhibited more potent activity than the parent PI-28. This is the first report on the effect of aryloxyacetylthioureas on a root parasitic weed and will contribute to the development of control reagents for root parasitic weeds.
RESUMO
A new class of propel- ler-shaped compound (4), which consisted of dehydrobenzo[14]annulene ([14]DBA) blades, as well as its naphtho homologues (5 and 6), have been prepared. Although NMR studies of compound 4 did not provide useful information regarding its conformation in solution, DFT calculations with different functionals and the 6-31G* basis set all indicated that the D(3)-symmetric structure was energetically more favorable than the C(2) conformer. From X-ray crystallographic analysis, it appeared that compound 4 adopted a propeller-shaped-, approximately D(3)-symmetric structure in the solid state, in which the [14]DBA blades were twisted substantially owing to steric repulsion between the neighboring benzene rings. On the contrary, in the case of compound 6, although the DFT calculations with the B3LYP functional predicted that the D(3)-symmetric conformation was more stable, calculations with the M05 and M05-2X functionals indicated that the C(2) conformer was more favorable because of π-π interactions between the naphthalene units of a pair of neighboring blades. Indeed, X-ray analysis of compound 6 showed that it adopted an approximately C(2)-symmetric conformation. Moreover, on the basis of variable-temperature (1)H NMR measurements, we found that compound 6 adopted a C(2) conformation and the barrier for interconversion between the C(2)-C(2) conformers was estimated to be 16.2 kcal mol(-1); however, no indication of the presence of the D(3) isomer was obtained. The relatively small energy barriers to interconversion, despite the large overlapping of neighboring blades, was ascribed to the flexibility of the acetylene linkages, which could be deformed substantially in the transition state of the ring-flip.
RESUMO
A novel combination of tetraphenyldiphosphine and diphenyl diselenide under photoirradiation conditions attains simultaneous introduction of diphenylphosphino and phenylseleno groups into carbon-carbon unsaturated bonds such as terminal alkynes or allenes, regioselectively.
RESUMO
We present here the results of studies of the synthesis and properties of donors and acceptors based on triangular dehydrobenzo[12]annulene ([12]DBA) system as a pi core. These studies were aimed at controlling the supramolecular crystal structure. Toward this end, the tricyano[12]DBA 2 and dodecafluoro[12]DBA ( 3) were synthesized as acceptors (A) and the tris(dialkylamino)[12]DBAs 4a-d as donors (D), and their electronic properties were determined by electronic absorption spectroscopy and electrochemical measurements. The main focus, though, was the formation of supramolecular structures in crystals. These compounds form distinct packing patterns as a result of the different intermolecular interactions. Tricyano[12]DBA 2 forms a two-dimensional (2D) sheet structure via hydrogen-bonding interactions, whereas a tilted-stack structure was found for 3 because of the lack of significant intermolecular interactions. Tris(dibutylamino)[12]DBA 4b exhibits a ladder-type 2D structure, probably because of van der Waals interactions between the butyl groups. The most significant finding is that charge-transfer interactions between donor 4a and acceptor 3 combined with their triangular molecular shapes and lateral CH...F hydrogen bonding result in the formation of a 2D rosette structure consisting of two different trimeric (DAD- and ADA-type) sandwich structures with 1:2 and 2:1 A/D ratios, respectively.
RESUMO
We present here the formation of a modular 2D molecular network composed of two different types of square-shaped butadiyne-bridged macrocycles, having intrinsic molecular voids, aligned alternately at the solid-liquid interface. Site-selective inclusion of a guest cation took place at every other molecular void in the molecular network with two different recognition sites.
RESUMO
A novel transition-metal-catalyzed hydrophosphination of terminal alkynes using a diphosphine-hydrosilane binary system takes place regioselectively to provide vinylic phosphines, which undergo air oxidation during workup, affording the corresponding vinylphosphine oxides in good yields. In this hydrophosphination, hydrosilanes act as a useful hydrogen source, and furthermore, small amounts of oxygen is required to accomplish the reaction efficiently.
RESUMO
Two-photon absorption (TPA) properties of two trefoil-shaped compounds with different edge linkages--tris(hexadehydrotribenzo[12]annulene) and tris(tetradehydrotribenzo[12]annulene)--and three asterisk-shaped compounds having no edge-linkage--hexakis(phenylethynyl)benzenes--are investigated experimentally by the open-aperture Z-scan and TPA-induced fluorescence methods with wavelength tuneable femtosecond pulses. The compound with ethynylene edge-linkage exhibits the most intense TPA (the maximal TPA cross section is 1300+/-170 GM at 572 nm where 1 GM=10(-50) cm(4) s molecule(-1) photon(-1)). The TPA activity of the compounds is primarily explained in terms of the planarity of the molecules in relation with the type of edge-linkage.
Assuntos
Alcinos/química , Benzeno/química , Físico-Química/métodos , Compostos Policíclicos/química , Espectrometria de Fluorescência/métodos , Derivados de Benzeno/química , Eletroquímica/métodos , Eletrônica , Hidrocarbonetos , Modelos Químicos , Conformação Molecular , Estrutura Molecular , Fótons , Fatores de TempoRESUMO
A simple, practical, and rapid access to quinoxalin-2-ones 1, 1,2,3,4-tetrahydroquinoxalines 2, quinoxalines 3, and quinoxalin-2(1H)-ones 4 has been achieved, based on the copper-catalyzed quinoxalinone formation of 2-haloanilines and amino acids followed by their reduction and oxidation. The olfactory properties and lipid accumulation inhibitory activity in cultured hepatocytes of the quinoxaline derivatives were also evaluated.
RESUMO
[reaction: see text] Bridged phenylthienylethenes and dithienylethenes were synthesized via Pd-catalyzed double-cyclization reactions of (Z,Z)-1,6-diaryl-1,5-hexadien-3-ynes. Pd-catalyzed as well as photoinduced Z/E isomerization of the products were also investigated.
RESUMO
[reaction: see text] Trefoil-shaped tris(hexadehydrotribenzo[12]annulene) possessing a substructure of the ultimate two-dimensional C(sp)-C(sp(2)) network, graphyne, and the related tris(tetradehydrotribenzo[12]annulene) were synthesized, and their ground- and excited-state properties were investigated.
RESUMO
[reaction: see text] Synthesis of aromatic ring substituted (E)-1,1'-biindenylidene derivatives was achieved by a domino-Heck type double cyclization of (Z,Z)-1,6-diaryl-1,5-hexadien-3-ynes.
RESUMO
The smallest [n.n]cyclophyne known, [12.12]paracyclophanedodecaynes C36 H8 and C36 Cl8 , were generated by [2+2] cycloreversion of its precursor under photolytic and mass spectrometric conditions. The stepwise loss of chlorine atoms from the anion of the octachloro derivative C36 Cl8- produced a carbon cluster anion C36- in the gas phase.