Selective synthesis of 3-formylbenzofuran and 3-acylbenzofuran using a chalcone rearrangement strategy.

We developed a method for highly selective synthesis of two benzofuran isomers, by rearranging and subsequently transforming 2-hydroxychalcones. Depending on the reaction conditions, synthesis of 3-formylbenzofurans, unconventional products, and 3-acylbenzofurans was achieved through cyclized 2,3-dihydrobenzofurans obtained from the rearranged products. The facile synthesis of 3-formylbenzofurans facilitated synthesis of the natural product, puerariafuran, from the corresponding chalcone.

Direct Synthesis of Chalcones from Anilides with Phenyl Vinyl Ketones by Oxidative Coupling Through C-H Bond Activation.

A novel approach for synthesizing chalcones by Pd-catalyzed oxidative coupling is described. This is the first report of the efficient coupling reaction of acetanilides with phenyl vinyl ketones under mild conditions. Selective C-H activation occurred next to the acetamide group to afford 2-aminochalcone derivatives.

A mild method for synthesizing carboxylic acids by oxidation of aldoximes using hypervalent iodine reagents.

A mild oxidation method for the conversion of aldoximes to carboxylic acids was developed mediated by hypervalent iodine reagents. This method covers a wide range of functionalized aldoximes and proceeds under mild conditions, utilizing PhI(OH)OTs as an oxidant.

Synthesis of 3-acylindoles by oxidative rearrangement of 2-aminochalcones using a hypervalent iodine reagent and cyclization sequence.

An efficient one-pot method was developed for the construction of 3-acylindoles via oxidative rearrangement of 2-aminochalcones followed by intramolecular cyclization. The reaction was used to convert a variety of 2-aminochalcones into 3-acylindoles in moderate to high yields.

Transformation of Methylene Acetals to Bromoformates with a Combination of Trimethyl(phenylthio)silane and N-Bromosuccinimide.

A novel transformation reaction of methylene acetals, using a combination of trimethyl(phenylthio)silane (PhSTMS) and N-bromosuccinimide (NBS) under mild reaction conditions, is described. Various methylene acetals were converted to their corresponding bromoformates in good to high yields. Under the given conditions, the reaction proceeded via a radical pathway.

[Cu(OH)(TMEDA)]₂Cl₂-catalyzed regioselective 2-arylation of 5-substituted tetrazoles with boronic acids under mild conditions.

A mild and regioselective 2-arylation of 5-substituted tetrazoles is described. The reaction proceeds regioselectively with a variety of arylboronic acids in the presence of [Cu(OH)(TMEDA)]2Cl2 to afford 2,5-disubstituted tetrazoles. This is the first report of highly regioselective arylation of 5-alkyltetrazoles.

Evaluation of acid-labile S-protecting groups to prevent Cys racemization in Fmoc solid-phase peptide synthesis.

Phosphonium and uronium salt-based reagents enable efficient and effective coupling reactions and are indispensable in peptide chemistry, especially in machine-assisted SPPS. However, after the activating and coupling steps with these reagents in the presence of tertiary amines, Fmoc derivatives of Cys are known to be considerably racemized during their incorporation. To avoid this side reaction, a coupling method mediated by phosphonium/uronium reagents with a weaker base, such as 2,4,6-trimethylpyridine, than the ordinarily used DIEA or that by carbodiimide has been recommended.

Synthesis and application of Nα-Fmoc-Nπ-4-methoxybenzyloxymethylhistidine in solid phase peptide synthesis.

The 4-methoxybenzyloxymethyl (MBom) group was introduced at the Nπ-position of the histidine (His) residue by using a regioselective procedure, and its utility was examined under standard conditions used for the conventional and the microwave (MW)-assisted solid phase peptide synthesis (SPPS) with 9-fluorenylmethyoxycarbonyl (Fmoc) chemistry. The Nπ-MBom group fulfilling the requirements for the Fmoc strategy was found to prevent side-chain-induced racemization during incorporation of the His residue even in the case of MW-assisted SPPS performed at a high temperature. In particular, the MBom group proved to be a suitable protecting group for the convergent synthesis because it remains attached to the imidazole ring during detachment of the protected His-containing peptide segments from acid-sensitive linkers by treatment with a weak acid such as 1% trifluoroacetic acid in dichloromethane.

Enzymatic stability of 2'-ethylcarbonate-linked paclitaxel in serum and conversion to paclitaxel by rabbit liver carboxylesterase for use in prodrug/enzyme therapy.

In prodrug/enzyme therapy for cancer, information on the sensitivity of hydrolytic enzymes to prodrug is required to reduce adverse effects of the parental drug and to find the activating enzyme. The aim of this study was to characterize the enzymatic stability of 2'-ethylcarbonate-linked paclitaxel (TAX-2'-Et) in the sera of several different species including humans. TAX-2'-Et disposition in serum was kinetically analysed using models with hydrolytic and/or degradation processes.

Paclitaxel-2'-Ethylcarbonate prodrug can circumvent P-glycoprotein-mediated cellular efflux to increase drug cytotoxicity.

Purpose: The aim of the study was to investigate whether 2'-ethylcarbonate-linked paclitaxel (TAX-2'-Et) circumvents P-glycoprotein (P-gp)-mediated cellular efflux and cytotoxicity enhanced by TAX-2'-Et activation within human culture cells transfected with a rabbit liver carboxylesterase (Ra-CES) cDNA.

Materials And Methods: TAX-2'-Et transport was characterized in a human colon carcinoma cell line (Caco-2) and paclitaxel (TAX)-resistant ovarian carcinoma cells (SKOV3/TAX60). Expression of P-gp, multidrug resistance protein (MRP) 2 and Ra-CES was detected by Western blotting.

Different effects of optical isomers of the 5-HT1A receptor antagonist pyrapyridolol against postischemic guinea-pig myocardial dysfunction and apoptosis through the mitochondrial permeability transition pore.

The recovery (%) of the left ventricular developed pressure by (S)-(-)-pyrapyridolol (5 x 10(-8) M) (90.7%), an optical isomer of a new 5-HT1A receptor antagonist, was greater than that by (R)-(+)-pyrapyridolol (66.2%, control: 34.

Capturing of acidic macromolecules from biological samples using a temperature-responsive polymer modified with poly-l-lysine.

We synthesized a temperature-responsive polymer, N-(isopropylacrylamide)-methacrylic acid copolymer, to which poly-l-lysine was introduced. The synthesized polymer as well as the parent polymer showed reversible soluble-insoluble changes in response to temperature changes across the lower critical solution temperature at 32 degree C in an aqueous solution. We found that the polymer efficiently captured acidic bio-macromolecules such as RNA, glycosaminoglycans and mucin-type glycoproteins in biological samples, and the captured molecules were recovered using aqueous NaCl solutions at high concentration.