Letters in Organic Chemistry - Volume 5, Issue 7, 2008

A simple method is reported to synthesize an anticancer drug, NCX 4040, conveniently in mild conditions using silicon chemistry. A starting material, 4-hydroxybenzyl alcohol, was silylated selectively first to give tbutyldimethylsilyl 4-hydroxybenzyl ether, which was then converted to NCX 4040 by esterification, desilylation, hydrochlorination and nitration.

The pheromone components of the legume pod borer, (E,E)-10,12-hexadecadienal, and the soybean pod borer, (E,E)-8,10-dodecadienyl acetate, were synthesized in good yields via Suzuki-Miyaura cross-coupling reactions.

Sonogashira reaction has been successfully applied to the synthesis of a series of 5-(carbohydrate-ethynyl)-2'- deoxyuridines for the first time. The synthetic route is general, high-yielding and compatible with the readily removable protecting group.

The exposure of solutions of 6,13-dithienylpentacenes to sunlight in air afforded their endoperoxides. The solutions and thin films of the endoperoxides were irradiated with UV light to reproduce the 6,13-dithienylpentacenes. These conversions are of interest as an ecological film-formation technology in the study of organic semiconductors.

A facile, efficient and high-yielding two-step synthesis of 3-oxo-5-arylthiopentanoates - the precursors for Nazarov reagent - from low-cost bench top chemicals like thiophenols, acrylonitrile, zinc and ethyl bromoacetate via the Blaise reaction, is reported.

A strategy for the synthesis of 8-vinylcatechin was developed, which involves (+)-catechin silylation with TBDMS-Cl, followed by bromination with NBS, a cross-coupling Suzuki reaction with vinylboronic acid pinacol ester and cleavage of TBDMS groups with TBAF, affording the 8-vinylcatechin.

A new thiophene analog of confusarine was synthesized by the use of Wittig reaction and radical cyclisation or photocyclisation.

Addition of an isocyanide to an iminium ion intermediate that forms from the reaction between an aromatic aldehyde and dibenzylamine, leads to formation of sterically congested 2-(dibenzylamino)-2-aryl acetamide derivatives in the presence of silica gel powder.

Quantitative structure activity relationships were developed for seventeen propenone derivatives reported in the literature that act as dual COX and 5-LOX inhibitors. Predominantly spatial, thermodynamic, topological, and electronic descriptors appear in the models. Docking between these compounds and COX-1, COX-2 and 5-LOX enzymes was also performed and mathematical relationships were developed between the binding energy and activity.

An easy electrochemical synthesis of 2-amino-4-aryl-3-cyano-5-ethoxycarbonyl-6-methyl-4H-pyrans has been set up, by galvanostatic electrolysis of a mixture of arylidenemalononitrile and ethyl acetoacetate in the absence of supporting electrolyte. Very high yields are obtained by a particularly simple procedure.

The first three-component coupling reactions between various anilines (1), benzaldehydes (2), and cyclohexen- 2-one (3) were performed under mild conditions (acetonitrile, room temperature, 14 h) in the presence of 20 mol % BiCl3 to obtain new 2,3-diaryl-2-aza[2.2.2]octan-5-ones (4,5) with interesting acetylcholinesterase inhibitory properties.

p-Nitrobenzylphosphonic acid was obtained via a nucleophilic substitution of nitrobenzyl bromide with trimethyl phosphite as opposed to nitration of benzylphosphonic acid. This compound is a competitive inhibitor of alkaline phosphatase (KI ∼ 125 μM) and has potential to inhibit a wide range of other phosphatases including serine/threonine phosphatases and tyrosine phosphatases.

Some interesting pyrrole derivatives were synthesized in moderate to high yields by coupling of 4- hydroxyproline with isatins, 11H-indeno[1,2-b]quinoxalin-11-ones, quinones and 9H-fluoren-9-one, in the presence of catalytic amount of Alum supported on silica gel (Alum-SiO2), under microwave irradiation.

Reactions of 5,6-di-(2`-furyl)-3-oxo-2,3-dihydropyridazin-4-carbonitrile (1) with Wittig-Horner reagents were investigated under microwave irradiation, and the effect of basic catalysis. The methodology afforded moderate to high yields of fused heterocycles bearing a phosphonate ester and / or phosphor-containing fused heterocycles. Bioassay results showed that the antibiotic activity of the new synthesized phosphorus compounds is significantly high when compared to available Streptomycin and Mycostatin (standard).

The fucosyltransferase-catalyzed 5-thiofucosylation reaction suffered from limitations in the β-selective synthesis of GDP-5-thiofucose, a donor substrate. We found that the use of electronegatively-substituted benzoate groups for 5-thiofucose protection improved the β-selectivity in the phosphorylation step. We thus achieved the synthesis of 5-thio-β- L-fucosyl phosphate in 50% yield from 5-thiofucose, using the 3,5-dinitrobenzoyl group.

Improved synthesis of 7,11-diarylspiro[5.5]undecane-1,9-dione via double Michael condensation of 1,5- bisaryl-1,4-pentadien-3-one with cyclohexanone was carried out in 51-96% yields for 3-12 h in CH2Cl2-H2O in the presence of phase-transfer catalyst under ultrasound irradiation. In comparison with reported methods, the main advantages of the present procedure are shorter reaction time and higher yields.

Irradiation of hyperforin in acetonitrile gave a single degradation product with a first order kinetics (k = 3.23 M h-1). The degradation product was a 1:1 tautomeric mixture of 2-methyl-3-hydroxy-4-(1-oxo-2-methyl-1-propyl)-1,5- dioxo-6-(3methyl-1-but-2-enyl)-2-cyclohexene and 2-methyl-1,3,5-trioxo-4-(1-hydroxy-2-methyl-1-propylene)-6-(3-methyl- 1-but-2-enyl)-cyclohexane. The product can also be obtained through three Norrish II reactions, followed by a fragmentation reaction.

Cross-couplings of 2-tributylstannyl-N-Boc-2,3-dehydropiperidine, a six-membered cyclic enecarbamate, with aryl iodides and triflates are reported for the first time. Under the Pd(0)/AsPh3 catalytic system (Farina's conditions), better conversions of this challenging substrate into the expected products were achieved with shorter reactions carried out under higher temperature.

The Zn-promoted direct reduction of ketones into the corresponding alcohols with silane under solvent-free conditions was reported. With ZnI2 as a catalyst, hydrosilylation of a large variety of ketones with silanes could proceed smoothly in the air, and exhibit excellent rates and high conversions.

A new two-step, one-pot alternative protocol for preparation of 1H-pyrazole-5-amines from 3-oxoalkanenitriles utilizing readily available acetylhydrazine has been developed. Typical by-products formed in traditional reactions of 3- oxoalkanenitriles with hydrazine are not formed when the present method is used, thus facilitating purification on a large scale. The method was used to prepare a medicinally important heterocycle on a kilogram scale.