Synthesis of pyrylium salts and pyridines containing heterocyclic substituents

A method of synthesizing pyrylium salts with heterocyclic substituents in the ring, has been investigated. The synthesis was carried out in two stages: alkaline condensation of aromatic and heterocyclic aldehydes with methyl ketones to give 1, 5-diketones, followed by cyclization to pyrylium salts by treatment with triphenylmethyl perchlorate. Pyridines containing heterocyclic substituents were obtained by treating the pyrylium salts with ammonia.     

(N‐heterocyclic carbene)PdCl(N‐heterocyclic carboxylate) complexes: Synthesis and catalytic activities towards arylation of benzoxazoles with aryl halides

A series of N‐heterocyclic carboxylate‐stabilized N‐heterocyclic carbene palladium complexes have been synthesized and fully characterized. The solid‐state structures indicate that each of the palladium centers is coordinated by an N‐heterocyclic carbene, a chloride and a bidentate N,O‐donor N‐heterocyclic carboxylate ligand. The catalytic performance of the complexes was screened and the results revealed that the complexes exhibit moderate to high catalytic activities for the direct C─H bond arylation of benzoxazoles with aryl bromides.     

A New Pathway to Synthesize Cyclomercurated Ferrocenylimines Containing Heterocyclic Ring

The cyclomercurated ferrocenylimines containing heterocyclic ring were prepared by the condensation of cyclomercuration of acylferrocene with the appropriate heterocyclic amine.This procedure provides an efficient method for the synthesis of cyclomerucurated ferrocenylimines containing heterocyclic ring which are difficultly synthesized by the conventional method.The reaction mechanism is proposed.     

Spectrophotometric and spectrofluorimetric studies of novel heterocyclic Schiff base dyes

Novel heterocyclic Schiff base dyes were prepared by the reaction of salicylaldehyde/2-Hydroxy-1-naphthaldehyde with different heterocyclic amines. Results of the newly synthesized compounds established by FT-IR, ¹H-NMR, ¹³C-NMR and GC–MS spectroscopic experiments were consistent with their chemical structures. Resulted heterocyclic Schiff base dyes were found to be pure from data obtained by the elemental analysis. In addition, spectrophotometric and spectrofluorimetric studies showed that these dyes were good absorbent and fluorescent. Fluorescence polarity study data revealed that some of these compounds were sensitive to the polarity of the microenvironment provided by different solvents. Time-based fluorescence steady-state measurements also showed that these heterocyclic Schiff base dyes have high photostability against photobleaching.     

Synthesis of difluorinated β-ketosulfones and novel gem-difluoromethylsulfone-containing heterocycles as fluorinated building blocks

A series of new heterocyclic β-ketosulfides was prepared by the reaction of the corresponding heterocyclic thiols with α-bromoacetophenone and its derivatives. Oxidation of the products using m-CPBA gave the corresponding heterocyclic β-ketosulfones, which, on treatment with Selectfluor™ under anhydrous condition underwent electrophilic fluorination resulting in new heterocycles with difluoromethylene moiety adjacent to the sulfur atom and the carbonyl group. Base-induced cleavage of the five types of the resulting products, with different heterocyclic moieties as model compounds, afforded the difluoromethyl sulfones attached to the corresponding heterocycles. They can be considered as interesting fluorinated building blocks for further elaborations.     

Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety,Privileged Hybrids in Anticancer Drug Discovery

Pentacyclic triterpenoids are well-known phytochemicals with various biological activities commonly found in plants as secondary metabolites. The wide range of biological activities exhibited by triterpenoids has made them the most valuable sources of pharmacological agents. A number of novel triterpenoid derivatives with many skeletal modifications have been developed. The most important modifications are the formation of analogues or derivatives with nitrogen-containing heterocyclic scaffolds. The derivatives with nitrogen-containing heterocyclic compounds are among the most promising candidate for the development of novel therapeutic drugs. About 75% of FDA-approved drugs are nitrogen-containing heterocyclic moieties. The unique properties of heterocyclic compounds have encouraged many researchers to develop new triterpenoid analogous with pharmacological activities. In this review, we discuss recent advances of nitrogen-containing heterocyclic triterpenoids as potential therapeutic agents. This comprehensive review will assist medicinal chemists to understand new strategies that can result in the development of compounds with potential therapeutic efficacy.     

异色满酮-4及其衍生物的合成IX异香豆素并杂环化合物的合成

本文通过3, 4-二氢异苯并吡喃酮-4和其β-二酮衍生物的缩合反应, 合成出3, 4-二氢异苯并吡喃并吲哚、并喹啉、并吡唑和并嘧啶类化合物, 并进一步氧化成标题化合物。所合成的新化合物均经核磁共振光谱红外光谱及元素分析证明其分子结构。     

Synthesis of regioisomeric 6,9-(chlorofluoro)-substituted benzo[g]quinoline-5,10-diones,benzo[g] isoquinoline-5,10-diones and 6-chloro-9-fluorobenzo[g]quinoxaline-5,10-dione

Treatment of difluoro or chloro fluoro-substituted benzyl bromides 5a-c with zinc dust in tetrahydro-furan leads to the corresponding benzylic zinc bromides 6a-c. These organometallics on treatment with chlorosubstituted heterocyclic esters 4A and 4B mediated by nickel catalysis undergo couplings to yield dihalobenzyl substituted heterocyclic esters 7Aa-c and 7Ba-c. Treatment of 4c with 6c under Pd catalysis leads to 7Cc. The acids 8, prepared by hydrolysis of these esters, with treatment of fuming sulfuric acid undergo cyclizations and oxidations to yield the desired regioisomeric dihalo-substituted heterocyclic quinones 2.     

Chromatographic methods for the analysis of heterocyclic amine food mutagens/carcinogens.

A series of potent heterocyclic amines that are mutagenic and carcinogenic have been discovered that are formed in some heated foods, most notably, meats derived from muscle. Determining the heterocyclic amine content in foods and food products is required for toxicological research, industry quality control, and possibly in the future, regulatory control. The contents of food needs to be determined using reliable analytical techniques. Since heterocyclic amines are present in foods at ng/g levels, a variety of liquid-liquid or solid-phase purification techniques are required, followed by gas or high-performance liquid chromatography. Peak detection has been successful using UV, fluorescence, and mass spectrometric detection, and biological activity using the Ames/Salmonella test. The low levels present require that chromatographic efficiency, and both detector sensitivity and selectivity be optimized. The cartridge solid-phase extraction and high-performance liquid chromatography method have been used to measure the known food-derived heterocyclic amines for several types of food, and to the authors knowledge, this is the only method undergoing intralaboratory comparison and validation. Our analysis of the literature shows that chromatographic analysis of the heterocyclic amines by high-performance liquid chromatography or gas chromatography (with derivatization) is satisfactory for heterocyclic amine analysis in foods although the methods are just now being optimized for routine use. The biggest improvements in speed and accuracy will probably come from improved extraction methods as analysis of complex food samples for heterocyclic amines will always be a challenge.     

AROMATIC AND HETEROCYCLIC DINITRILES AND THEIR POLYMERS. Ⅺ. STUDY ON THE POLYMERIZATION OF AROMATIC AND HETEROCYCLIC DINITRILES BY INFRARED SPECTROSCOPY*

The polymerization rates of fourteen aromatic and heterocyclic dinitriles were measured by infraredspectroscopy and compared with that of 4, 4′-biphenyldicarbonitrile. The rate is greatly enhancedwhen an electron withdrawing group is substituted at the para position of cyano group in aromaticdinitriles. The polymerization rates of heterocyclic dinitriles wer discussed in terms of π-lectrondensity of the heterocyclic rings.     

过渡金属催化合成含氮杂环化合物的研究进展

含氮杂环化合物是一类非常重要的有机杂环化合物,也是有机合成化学的研究热点之一。本文首先简要介绍了含氮杂环化合物在天然产物、合成药物和功能材料中的分布及其广泛应用;然后以不同过渡金属催化剂为线索,按照时间由远至近的顺序分别概述了Pd、Ag、Fe、Ni、Zn、Cu等六类过渡金属催化剂在合成五、六元含氮杂环化合物方面的研究进展,对反应条件、反应特征进行了概括;最后对含氮杂环化合物合成领域的过渡金属催化剂的整体发展趋势进行了归纳总结。     

The Synthesis of Substituted 2-Aminophenyl Heterocyclic Ketones

The synthesis of substituted 2-aminophenyl heterocyclic ketones, key intermediates to the preparation of 1,4-benzodiazepines has been achieved in one step and in good, yield from the corresponding anthranilic acid, by treatment with heterocyclic lithium reagents and chlorotrimethylsilane.     

The reaction of heteroaroyl‐substituted heterocyclic ketene aminals with 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl azide

The reaction of heteroaroyl‐substituted heterocyclic ketene aminals with 2,3,4,6‐tetra‐O‐acetyl‐β‐D ‐glucopyranosyl azide was investigated and a series of potential bioactive compounds, 1‐glucopyranosyl‐4‐heterocyclic‐5‐heteroaryl‐1,2,3‐triazoles, were obtained in good yields. Both the reaction rate and the yield were strongly affected by the heteroaryl and heterocyclic groups. In order to improve their water solubility, the deprotection of 1‐glucopyranosyl‐4‐heterocyclic‐5‐heteroaryl‐1,2,3‐triazole was carried out. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:242–247, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10023     

Blue Chitin Columns for the Extraction of Heterocyclic Amines from Urine Samples

During normal cooking of meat, a class of mutagenic/carcinogenic compounds called heterocyclic amines is formed. Heterocyclic amines are rapidly absorbed and metabolised in the human body, and for estimation of the intake of heterocyclic amines, it is useful to determinate their levels in the urine. Blue Chitin columns were used for the extraction and purification of heterocyclic amines from urine samples spiked with 14 different heterocyclic amines. The samples were analysed using LC-MS. The results show that Blue Chitin columns provide a straightforward and rapid means of extracting heterocyclic amines from urine samples, and that Blue Chitin column are also useful in the purification of urinary metabolites.     

Spectroscopic study of rigid-rod polymers. II. Protonation effect

The protonation of a heterocyclic rigid-rod polymer poly(p-phenylene benzbisthiazole) and its model compound has been studied by UV-visible and Raman spectroscopy. Because of the two nitrogens on the heterocyclic ring, spectroscopic features of unprotonated, half-protonated, and fully protonated structures have been identified. For the fully protonated molecule, there is also an increase in conjugation between the phenyl ring and the heterocyclic ring.     

Solid-phase synthesis of heterocyclic nucleoside analogues: substituted uracils tethered to isoxazoles, isoxazolines, and triazoles from a selenopolystyrene resin

A heterocyclic nucleoside analogue library of uracils N1 tethered to isoxazoles, isoxazolines, and triazoles and uracil N3 tethered to isoxazolines and isoxazoles was constructed by solid-phase organic synthesis. This strategy opens the way for the generation of small libraries of heterocyclic nucleoside analogues for biological screening.     

Combinatorial libraries of bis-heterocyclic compounds with skeletal diversity

Combinatorial solid-phase synthesis of bis-heterocyclic compounds, characterized by the presence of two heterocyclic cores connected by a spacer of variable length/structure, provided structurally heterogeneous libraries with skeletal diversity. Both heterocyclic rings were assembled on resin in a combinatorial fashion.     

Efficient Synthesis of Chromone and Flavonoid Derivatives with Diverse Heterocyclic Units

Chromones and flavonoids are important bioactive compounds. We envisioned that new heterocyclic‐substituted chromones or flavonoids might act as new bioactive compounds. To obtain diverse molecules, we developed an efficient one‐pot synthesis by Michael aldol reaction of chromone and flavonoid derivatives bearing heterocyclic units. The 2,3‐heterocyclic‐substituted chromones were obtained in one step. Moreover, the use of substituted benzaldehydes and subsequent addition of heterocyclic aldehydes gave 3‐pyridyl‐substituted flavones. We also examined these one‐pot reactions in the solid phase. To introduce an additional point of diversity into the molecules, Suzuki–Miyaura coupling was performed. Furthermore, we identified the cytotoxicity of the synthesized compounds against cancer cells (PANC1 and HeLa cells). Several compounds were cytotoxic to these cancer cells.     

Synthesis of Novel [1,2,4]Triazolo[3,4-d][1,5] Benzodiazepinones Derivatives by 1,3-Dipolar Cycloaddition

Cycloaddition of N-aryl-C-ethoxycarbonylnitrilimines and diarylnitrilimines on 1,5-benzodiazepinones was achieved in a one-pot procedure, to give a variety of compounds possessing an additional heterocyclic ring fused to the heterocyclic nucleus. This reaction was revealed to be completely peri and regioselective. The structures were elucidated by spectral methods and X-ray crystallographic analysis.