Determination of binding modes and binding constants for the complexes of 6H-pyrido[4,3-b]carbazole derivatives with DNA.

The binding modes and binding constants for the complexes of forty types of pyridocarbazole derivatives 1-40 with double stranded DNAs (dsDNAs) were reported. The binding modes were determined by a combination of a deflection spectroscopy and orientation of the corresponding molecule in the DNA-based film with chain alignment. All of the compounds exhibited the intercalation-binding mode. Its binding constants Ka for the complexes, determined by quartz crystal microbalance (QCM), varied from 1.7×105 to 4.5×107M-1 according to the substituents on the pyridocarbazole framework and the sequences of dsDNA. The binding constants Ka of pyridocarbazole derivatives possessing the 2-(ω-amino)alkyl group and 5-(ω-amino)alkylcarbamyl group were larger than those of the corresponding ω-ureido derivatives. These ω-amino compounds exhibited strong GC base-pair preference in complexation. The Ka values decreased with the increasing NaCl concentration. It was clarified by a molecular modeling that the framework of the 2-tethered ω-amino derivative was completely overlapped with the stacking GC base-pairs leading to the formation of the stable intercalative-complex, and that the framework of the 5-tethered ureido derivative was half overlapped leading to the formation of the unstable complex. Furthermore, there were good linear relationships between lnKa and the relative stabilities Srel of the complexes. Contrary to our expectation, there was no linear relationship between lnKa and IC50 against Sarcoma-180, NIH3T3, and HeLa S-3 cell lines.

Oxidative Coupling of Terminal Alkynes with Aldehydes Leading to Alkynyl Ketones by Using Indium(III) Bromide.

An indium(III)-promoted direct acylation of terminal alkynes using aldehydes leading to ynones was developed. In contrast to the previous addition reactions of alkynes to aldehydes, which provide propargylic alcohols, the oxidative coupling proceeded exclusively to afford alkynyl ketones. The products were likely generated through an Oppenauer oxidation of the indium propargylic alkoxide species by excess amounts of aldehydes.

Gallium-catalyzed reductive chlorination of carboxylic acids with copper(II) chloride.

Described herein is the direct chlorination of carboxylic acids using copper(II) chloride via a gallium(III)-catalyzed reduction in the presence of a hydrosiloxane. During this reductive chlorination, the counteranions of CuCl2 functioned as a chloride source.

Synthesis and in vitro antitumor activity of novel 2-alkyl-5-methoxycarbonyl-11-methyl-6H-pyrido[4,3-b]carbazol-2-ium and 2-alkylellipticin-2-ium chloride derivatives.

Twenty-one types of novel ellipticine derivatives and pyridocarbazoles (5-methoxycarbonyl-11-methyl-6H-pyrido[4,3-b]carbazoles) with a nitrosourea moiety, linked by an oxydiethylene unit at the 2 position, were synthesized, and their cytotoxicity against HeLa S-3 cells was evaluated. Some of these new compounds exhibited potent antitumor activity by comparison with that of ellipticine.

Indium(III)-catalyzed reductive bromination and iodination of carboxylic acids to alkyl bromides and iodides: scope, mechanism, and one-pot transformation to alkyl halides and amine derivatives.

Highly effective indium(III)-catalyzed reductive bromination or iodination of a variety of carboxylic acids with 1,1,3,3-tetramethyldisiloxane (TMDS) and a source of bromine or iodine is described. This functional group interconversion has high tolerance for several functional groups, such as halogens, a hydroxy group, a nitro group, an olefin part, and a sulfide moiety. This indium catalytic system is also applicable to the reductive iodination of aldehyded, acyl chlorides, and esters. Furthermore, this reducing system can be applied to the one-pot synthesis of alkyl halides and amine derivatives via the addition of nucleophiles. Insight into the reaction mechanism was gained via the time course of (1)H and (13)C NMR monitoring experiments and the corresponding stepwise reactions.

Copper-catalyzed three- five- or seven-component coupling reactions: the selective synthesis of cyanomethylamines, N,N-bis(cyanomethyl)amines and N,N'-bis(cyanomethyl)methylenediamines based on a Strecker-type synthesis.

We have demonstrated that a cooperative catalytic system comprised of CuCl and Cu(OTf)(2) could be used to effectively catalyse the three-, five- and seven-component coupling reactions of aliphatic or aromatic amines, formaldehyde, and trimethylsilyl cyanide (TMSCN), and selectively produce in good yields the corresponding cyanomethylamines, N,N-bis(cyanomethyl)amines and N,N'-bis(cyanomethyl)methylenediamines.

Indium-catalyzed reductive bromination of carboxylic acids leading to alkyl bromides.

The combination of 1,1,3,3-tetramethyldisiloxane (TMDS) and trimethylbromosilane (Me(3)SiBr) with a catalytic amount of indium bromide (InBr(3)) undertook direct bromination of carboxylic acids, which produced the corresponding alkyl bromides in good to excellent yields. The reducing system was tolerant to several functional groups.

Single-step thioetherification by indium-catalyzed reductive coupling of carboxylic acids with thiols.

Direct thioetherification from a variety of aromatic carboxylic acids and thiols using a reducing system combined with InBr(3) and 1,1,3,3-teramethyldisiloxane (TMDS) in a one-pot procedure is demonstrated. It was also found that a system combined with InI(3) and TMDS underwent thioetherification of aliphatic carboxylic acids with thiols.

Structure-activity relationship in the antitumor activity of 6-, 8- or 6,8-substituted 3-benzylamino-ß-carboline derivatives.

We synthesized 47 kinds of 3-amino- or 3-benzylamino-ß-carboline derivatives with a substituent on the 6-, 8-, or 6,8-carbon atoms and evaluated their antitumor activities for Hela S-3 and Sarcoma 180 cell lines using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Consequently, we succeeded to develop 3-benzylamino-8-methylamino-ß-carboline (17a) and 8-methylamino-3-(3-phenoxybenzyl)amino-ß-carboline (17c) with antitumor activity with IC(50) values of 0.046, 0.032 µM, respectively, against HeLa S-3 cell line, which are higher than that of previously reported 3-(3-phenoxybenzyl)amino-ß-carboline (10e) of 0.074 µM. Furthermore, effects of Cl group at 6-carbon atom on the type of cell death was evaluated using 3-benzylamino-6-chloro-ß-carboline (10b), 3-benzylamino-ß-carboline (10d), N-(3-benzylamino)-6-chloro-9H-ß-carbolin-8-yl)benzamide (14g), and N-(3-benzylamino-9H-ß-carbolin-8-yl)benzamide (17b) to show no effect. Hoechst 33342 staining and DNA fragmentation assay suggested that these compounds induced cell death by apoptosis. In addition, using flow cytometry analysis, we established that the cell death pathway was through the arrest of the cell cycle in the G(2)/M phase.

Copper-catalyzed [5+1] annulation of 2-ethynylanilines with an N,O-acetal leading to construction of quinoline derivatives.

A novel copper-catalyzed [5 + 1] annulation of 2-ethynylanilines with an N,O-acetal, which functioned as a C1 part, leading to the preparation of quinoline derivatives with an ester substituent on the 2-position is described. A combination of CuBr(2) and trifluoroacetic acid (TFA) promoting [5 + 1] annulation of the 2-ethynylaniline with ethyl glyoxylate is also demonstrated.