Wen-Cai Huang

Synthesis and evaluation of 2-[2-(phenylthiomethyl)-1H-benzo[d] imidazol-1-yl)acetohydrazide derivatives as antitumor agents.

A novel class of acetylhydrazone derivatives (5a-x) containing 2-(phenylthiomethyl)-1H-benzo-[d]-imidazole moieties are synthesizer, and their antitumor activities against A549, HCT116, HepG2, PC-9, and A375 were determined by the MTT assay. Among them are N-(2,4-dihydroxybenzylidene)-2-(2-(phenylthiomethyl)-1H-benzo[d]-imidazol-1-yl)acetohydrazide (5a) and N-(5-bromo-2-hydroxy-benzylidene)-2-(2-(phenylthiomethyl)-1H-benzo[d]-imidazol-1-yl)acetohydrazide (5d) which displayed excellent cancer inhibitory activity against the tested cancer cells (IC(50) 4-17 μM), compared with 5-FU and SU11248. The others have moderate to weak inhibitory activity against the tested cancer cell lines.

Highly efficient cyanoimidation of aldehydes.

Cyanoimidation of aldehydes using cyanamide as a nitrogen source and using NBS as an oxidant was achieved in high yields without the addition of a catalyst. The method has several advantages, including mild conditions, simple workflow, and inexpensive reagents. The reaction proceeds in a one-pot manner, giving rise to the formation of intermolecular C-N and C-O bonds. Subsequently, the substituted N-cyanobenimidate products may also undergo a cyclization reaction to give l,2,4-triazole derivatives in high yields.

Synthesis, antiproliferative activities and in vitro biological evaluation of novel benzofuransulfonamide derivatives.

In a cell-based screen of novel antiproliferative agents, the hit compound 1a, which bears a benzofuransulfonamide scaffold, exhibited broad-spectrum antiproliferative activities against a panel of tumor cell lines. The promising in vitro antiproliferative activity and structural novelty of 1a prompted us to investigate the synthesis of five analogs of 1a and test their antiproliferative activities. The most potent analogue, 1h, exhibited enhanced antiproliferative activities compared with the parent 1a, and exhibited an IC(50) value against NCI-H460 cells of 4.13 μM compared with 4.52 μM for the positive control cisplatin. Flow cytometric analysis revealed that 1h induces significant levels of apoptosis in NCI-H460 cells in vitro at low micromolar concentrations. These results suggest that 1a and analogs based on its benzofuransulfonamide scaffold may constitute a novel class of antiproliferative agents, which deserve further study.

Facile microwave-assisted synthesis of substituted benzofuran derivatives

A series of benzofuran derivatives have been synthesized by use of a microwave-assisted process. Substituted or unsubstituted ο-hydroxyacetophenone and salicylaldehyde reacted with ethyl bromoacetate, ω-bromoacetophenone, or chloroacetone under the action of potassium carbonate in DMF to yield substituted benzofuran derivatives. Compared with conventional heating, this microwave-assisted synthetic process has the advantages of more convenient operation, shorter reaction time, and higher yield.

Synthesis and evaluation of 2-(2-((4-substituted-phenoxy)methyl)-1H-benzo[d] imidazol-1-yl)acetohydrazone derivatives as antitumor agents

Abstract Twelve 2-(2-((4-substituted-phenoxy)methyl)-1H-benzo[d]imidazol-1-yl)-acetylhydrazone derivatives were synthesized. These synthesized compounds have been tested for their antitumor activity in vitro against A549, MDA-MB-231, A375, and HCT116 cancer cells using the MTT assay. Among them, the compounds containing hydroxyl on position 2 at phenyl of hydrazone displayed a good anticancer activity, especially those containing two hydroxyl on 2 and 4 place at phenyl of hydrazone, for example, N′-(2,4-dihydroxybenzylidene)-2-(2-((p-tolyloxy)methyl)-1H-benzo[d]imidazol-1-yl)acetohydrazide 7b, N′-(2,4-dihydroxybenzylidene)-2-(2-(phenoxymethyl)-1H-benzo[d]imidazol-1-yl) acetohydrazide 7f, 2-(2-((4-chlorophenoxy)methyl)-1H-benzo[d]imidazol-1-yl)-N′-(2,4-dihydroxybenzylidene)acetohydrazide 7j, have excellent antitumor activity. The results revealed that hydroxyl on position 2 at phenyl of hydrazone was necessary for anticancer activity, and another hydroxyl group on 4 place at phenyl can increase the inhibitory activity. An electron-withdrawing substituent at position 4 on phenyl ring of 2-phenoxylbenzimidazole was favorable to increasing anticancer activity toward MDA-MB-231, A375, and HCT116 cells.

Alkynylation of aldehydes mediated by zinc and allyl bromide: a practical synthesis of propargylic alcohols

A practical synthesis of propargylic alcohols was developed by alkynylation of aldehydes mediated by zinc and allyl bromide. Aromatic, aliphatic and vinyl aldehydes react with phenylacetylene or 1-hexyne to obtain various propargylic alcohols at room temperature in up to 98% yield. This method is characterized with inexpensive materials, wide substrate scope, and mild reaction conditions, and is also easy to scale up. In addition, this protocol is applicable to the alkynylation of α-ketone esters and epoxides to generate α-tertiary-hydroxy esters and α-alkynyl alcohols, respectively.Graphical Abstract

An Improved Preparation of 2,6-di-(t-Butyl)-4-methylphenol

As a typical sterically hindered phenolic anti-oxidant, 2,6-di-(t-butyl)-4-methylphenol, also known as butylated hydroxytoluene (or BHT), is widely used in rubber, plastic, paint, jet fuels, petroleum products, bio-diesel, cosmetics, food and pharmaceuticals due to its strong anti-oxidant power, low volatility and sturdiness. In addition, BHT has become important for the preparation of other compounds such as 3,5-di-(t-butyl)-4-hydroxybenzaldehyde, 3,5-di-(t-butyl)-4-hydroxybenzyl bromide and 2,6-di-(t-butyl)-1,4-benzoquinone. Recently, BHT has been shown to display anti-tumor and anti-oxidant activities and to be effective in protecting against hepato-toxicity. Thus BHT has also become a lead compound for the development of various drugs and an intermediate for the synthesis of other drugs or drug candidates. With its ever-increasing utility in the food and pharmaceutical industries, it is imperative to understand the nature and toxicity of impurities that might be produced during its manufacture in order to increase the purity of the BHT produced. Herein, we report a study on the reaction of p-cresol with isobutylene to prepare BHT. Over the past few decades, a considerable amount of work has been devoted to the use of novel acid catalysts such as ion exchange resins, phosphorus tungsten heteropoly acid, ionic liquids and AlCl3 supported on Montmorillonite 13 to perform the FriedelCrafts alkylation of p-cresol with isobutylene. Although many of these catalysts do exhibit desirable features such as minimal corrosion of the equipment, high selectivity, and recyclability, their high cost, variable catalytic activity, and long production cycle have limited their utilization on a large scale. In comparison, conc. sulfuric acid, has the advantages of high catalytic activity, low cost, and ready availability. Thus, it has been utilized widely in the production of BHT in spite of the fact that it can result in corrosion of the equipment and formation of impurities.

Synthesis, crystal structure and evaluation of cancer inhibitory activity of 4-[indol-3-yl-methylene]-1 H -pyrazol-5(4 H )-one derivatives

A series of 4-(1H-indol-3-yl-methylene)-1H-pyrazol-5(4H)-one derivatives have been synthesised. The Z structure of 4-[(1-methyl-1H-indol-3-yl)methylene]-3-phenyl-1-p-tolyl-1H-pyrazol-5-one was determined by X-ray crystallography. The antitumour activity was evaluated against five cancer cells by MTT assay. [(1H-Indol-3-yl)methylene]-1-(2,4-dini-trophenyl)-3-methyl-1H-pyrazole-5-one and 4-{4-[(1-benzyl-1H-indol-3-yl)methylene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl}-benzoic acid have similar anticancer activity with 5-UF on the test cancer cells (exception of A375). Almost all the target compounds displayed antitumour activity against A549 and PC-9, and those with benzyl at 1-position of indole had higher activity against PC-9 (IC50 value lower than 30 μM). Those with benzyl at the indole and carboxyl at the phenyl part of of pyrazole were more active against PC-9 and A549 cells, providing a good indication for subsequent optimisation as lung cancer inhibitory agents.

trans-4-(Tosyloxymethyl)cyclohexanecarboxylic acid

The title compound, C15H20O5S, is an intermediate in the synthesis of a new type of poly(amidoamine) (PAMAM) dendrimer. The cyclohexane ring exhibits a chair conformation, with C—C bond lengths in the range 1.518 (3)–1.531 (3) Å and C—C—C angles in the range 110.45 (19)–112.09 (19)°; these agree well with the values in other cyclohexane derivatives described in the literature. In the crystal structure, adjacent molecules are linked by O—H⋯·O hydrogen bonds. The H atoms of the methyl group are disordered equally over two positions.

trans-4-(Phenoxy­meth­yl)cyclo­hexane­carboxylic acid

The title compound, C14H18O3, is an important model compound in the synthesis of phenolic ethers. The cyclohexane ring adopts a chair conformation. In the crystal structure, adjacent molecules are linked by O—H⋯O hydrogen bonds.