A series of new 2-phenylbenzothiazoles has been synthesized on the basis of the discovery of the potent and selective in vitro antitumor properties of 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (8n; GW 610, NSC 721648). Synthesis of analogues substituted in the benzothiazole ring was achieved via the reaction of o-aminothiophenol disulfides with substituted benzaldehydes under reducing conditions. Compounds were evaluated in vitro in four human cancer cell lines, and compound 8n was found to possess exquisitely potent antiproliferative activity (GI(50) < 0.1 nM for MCF-7 and MDA 468). Potent and selective activity was also observed in the NCI 60 human cancer cell line panel. Structure-activity relationships established that the compound 8n stands on a pinnacle of potent activity, with most structural variations having a deactivating in vitro effect. Mechanistically, this new series of agents contrasts with the previously reported 2-(4-aminophenyl)benzothiazoles; compound 8n is not reliant on induction of CYP1A1 expression for antitumor activity.

Antitumor benzothiazoles. 26.(1) 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines.

Commercially available magnesium perchlorate is reported as an extremely efficient catalyst for the synthesis of α-aminophosphonates. A three-component reaction (3-CR) of an amine, an aldehyde or a ketone, and a di-/trialkyl phosphite (Kabachnik−Fields reaction) took place in one pot under solvent-free conditions to afford the corresponding α-aminophosphonates in high yields and short times. The use of solvent retards the rate of the reaction and requires a much longer reaction time than that for neat conditions. The reactions involving an aldehyde, an aromatic amine without any electron-withdrawing substituent, and a phosphite are carried out at rt. The reactions involving cyclic ketones, aromatic amines with an electron-withdrawing substituent, and aryl alkyl ketone (e.g., acetophenone) require longer reaction times at rt or heating. Magnesium perchlorate was found to be superior to other metal perchlorates and metal triflates during the reaction of 4-methoxybenzaldehyde, 2,4-dinitroaniline, and dimethy...

An extremely efficient three-component reaction of aldehydes/ ketones, amines, and phosphites (Kabachnik-Fields Reaction) for the synthesis of α-aminophosphonates catalyzed by magnesium perchlorate

Perchloric acid adsorbed on silica gel as a new, highly efficient, and versatile catalyst for acetylation of phenols, thiols, alcohols, and amines

Catalyst-Free Conjugated Addition of Thiols to α,β-Unsaturated Carbonyl Compounds in Water

Synthesis and biological evaluation of indolyl chalcones as antitumor agents

Electrostatic catalysis by ionic aggregates: scope and limitations of Mg(ClO4)2 as acylation catalyst

Commercially available LiOH·H2O was found to be a highly efficient dual activation catalyst for Claisen–Schmidt condensation of various aryl methyl ketones with aryl/heteroaryl aldehydes providing an easy synthesis of 1,3-diaryl-2-propenones under mild conditions. The reactions were carried out at room temperature and in short times affording high yields. Excellent chemoselectivity was observed with carbonyl substrates bearing halogen atom and nitro group without any competitive aromatic nucleophilic substitution. The resultant chalcones did not undergo Michael addition with the ketone enolate. The rate of Claisen–Schmidt condensation was found to be dependent on the steric and electronic factors of the carbonyl substrates.

LiOH·H2O as a novel dual activation catalyst for highly efficient and easy synthesis of 1,3-diaryl-2-propenones by Claisen–Schmidt condensation under mild conditions

Thiolate anions have been generated in a "demand-based" fashion under virtually neutral conditions for chemoselective deprotection of aryl alkyl ethers. Solvents play the critical role in making the reaction effective and should have high values of epsilon (>30), molecular polarizabilities (>10), and DN (>27) and low values of AN ( methyl > ethyl. Electron-withdrawing substituents increase the rate of ether cleavage reaction. The influence of the steric and electronic factors have been successfully exploited for selective deprotection of aryl alkyl ethers during inter- and intramolecular competitions.

Demand-based thiolate anion generation under virtually neutral conditions: influence of steric and electronic factors on chemo- and regioselective cleavage of aryl alkyl ethers.

The nucleophilicity of arenethiols can be augmented via hydrogen bonding with ‘naked' halide anion. The activity of the halide anions follow the order F- ≫ Cl- ∼ Br- ∼ I- and is dependent on the countercation (Bu4N ∼ Cs ∼ K > Na ≫ Li). The solvent plays an important role in nucleophilic activation as well as regeneration of the effective nucleophile (e.g. ArS-) and those with high dielectric constant, high molecular polarizability, high donor number (DN), and low acceptor number (AN) are the most effective. Selective deprotection of alkyl/aryl esters and aryl alkyl ethers can be achieved under nonhydrolytic and neutral conditions by the treatment with thiophenol in 1-methyl-2-pyrrolidone (NMP) in the presence of a catalytic amount of KF. Aryl esters are selectively deprotected in the presence of alkyl esters and alkyl methyl ethers during intramolecular competitions.

Influence of hydrogen bonding in the activation of nucleophiles: PhSH-(catalytic) KF in N-methyl-2-pyrrolidone as an efficient protocol for selective cleavage of alkyl/aryl esters and aryl alkyl ethers under nonhydrolytic and neutral conditions.

Phenolic esters are efficiently converted to 2-substituted benzothiazoles in a one-pot reaction by treatment with 2-aminothiophenol in the presence of a catalytic amount of K 2 CO 3 in N-methyl-2-pyrrolidone (NMP) at 100 °C.

Lalima Sharma

Papers

Electrostatic catalysis by ionic aggregates: scope and limitations of Mg(ClO4)2 as acylation catalyst

LiOH·H2O as a novel dual activation catalyst for highly efficient and easy synthesis of 1,3-diaryl-2-propenones by Claisen–Schmidt condensation under mild conditions

Demand-based thiolate anion generation under virtually neutral conditions: influence of steric and electronic factors on chemo- and regioselective cleavage of aryl alkyl ethers.

Influence of hydrogen bonding in the activation of nucleophiles: PhSH-(catalytic) KF in N-methyl-2-pyrrolidone as an efficient protocol for selective cleavage of alkyl/aryl esters and aryl alkyl ethers under nonhydrolytic and neutral conditions.

An Efficient Conversion of Phenolic Esters to Benzothiazoles under Mild and Virtually Neutral Conditions