Letters in Organic Chemistry - Volume 7, Issue 2, 2010

Samarium diiodide is an efficient Lewis acid type catalyst for the 1,4-addition of aromatic amines onto α,β- unsaturated N-benzoyl amides affording new β-amino amides. These reactions are compared with similar aza-Michael additions involving α,β-unsaturated-N-acyloxazolidinones.

Michael addition of aldehydes and ketones to trans-β-nitrostyrene catalyzed by L-proline was investigated using microwave heating for rapid optimization of reaction conditions. The products could be obtained, easily in very short reaction times, high yields and comparable diastereo- and enantioselectivity with respect to the original procedures, under simple and more environmentally benign conditions such as the use of ethanol as the solvent and only a slight excess of the carbonyl compound.

Varieties of heterocyclic compounds were prepared in good yield from 4-benzoyl-5-phenyl-2,3-dihydro-2,3- furandione under microwave irradiation conditions. The reaction revealed much shorter reaction times with comparable yields comparison to the corresponding thermal conditions.

A facile synthesis of 2-substituted-2-hydroxyindane-1,3-diones is reported via the reaction of diazoacetates with benzenemethanol and indane-1,2,3-triones catalyzed by dirhodium acetate.

The antipodes of racemic 1-phenyl-1,2-dihydrophosphinine oxides 1A and 1B were separated by resolution via formation of a diastereomeric complex using (-)-(2R,3R)-α,α,α',α'-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol (spiro-TADDOL) 2. The (+)-antipode of 1-phenyl-3-diphenylphosphinoyl-1,2,3,6-tetrahydrophosphinine oxide 3 was synthesized by the diastereoselective addition of diphenylphosphine oxide to the α,β-double-bond of (-)-1,2- dihydrophosphinine oxide 1A. The new chiral tetrahydrophosphinine oxide (+)-3 served, after double deoxygenation, as a novel P-chiral bidentate ligand in the corresponding platinum complex.

Direct experimental evidence for the priority of flexible ligand skeleton in asymmetric Friedel-Crafts alkylation was obtained through XRD analysis of flexible ligand/ZnCl2 complex, as well as synthesis of dihydroacridine-linked bis(oxazoline) ligands with planar rigid scaffold. A transition state model without NH…π interaction was proposed for the rigid ligands to interpret the inversion of absolute configuration.

New series of structure based on original benzodioxine and benzoxazine heterocycles were prepared leading to potential anticancer lead compounds. In this paper, we described a convenient approach via a Diels-Alder cycloaddition in order to efficiently provide three new indole isosteres in indolocarbazoles series. Their first cytotoxic evaluation was also reported.

We report the synthesis of novel polyether-based polyols derived from simple glycosides that bear sulfur spacers in the attempt to potentially provide new antibiotics. The CI-MS demonstrated the stepwise and successive fission of the sulfide-spacer groups; however, it does not distinguish between the alditols having different arrangement of O- (CH2)3-S(CH2)2OH groups. The investigated compounds exhibited antimicrobial activities against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and antifungal activities against Candida albicans at a concentration of 1 mg / ml in DMF.

There is an increased demand for significant amounts of carbohydrate based molecules for complete biological, medicinal, and pharmacological investigations where tremendous efforts have been made to develop novel and facile procedure for the synthesis of glycoconjugates and diverse carboxamides. Limitations with the common approaches for amide bond formation, including use of hazardous chemicals, long reaction times, low reaction yields, frequently require strong basic catalysts, strictly anhydrous conditions, harsh reaction conditions, expensive and limited availability of coupling materials, and moreover the less stability of activated acids warrant the search of a simple, short, and high yielding amide bond synthetic methodology. Herein, a facile and high yielding synthesis of novel glycosyl carboxamide with both furanose and pyranose sugar using benzotriazole methodology has been developed under mild conditions.

3-Bromoindolylmaleimide and bisindolylmaleimide were synthesized from succinimide in three steps sequnence consisting of bromination, N-methylation and indole addition in the presence of magnesium and bromoethane. They were subjeced to the regioselective amination with substituted amines to provide 3-aminoindolylmaleimides, 3- amino-N-alkylated indolylmaleimides and N-alkylated bisindolylmaleimides in good yields. The resulting indolylmaleimides represent a new class of potentially bioactive compounds.

An improved and scalable process for the production of rivastigmine tartrate is reported. The improved process provides rivastigmine tartrate at considerably lower cost and allows the omission of hazardous chemicals. The overall yield is increased from 4.66% (reported process) to 17% with the improved process.

In this paper we have designed different methods, according to the differences in nucleophilicity of amino, to conjugate tartaric acid or malic acid with two kinds of useful intermediates respectively via amide bond, envisaging they are promising matrix metalloproteinase inhibitors or anticancer medicine.

The resolution of 2-amino alcohols protected by urethane-type groups either via porcine pancreatic lipase (PPL) hydrolysis of the corresponding racemic acetates or via PPL catalyzed transesterification of racemic alcohols was studied. In both cases, Boc protecting group led to better chemical yields and enantiopurities than Z and Fmoc protecting groups. Furthermore, a simple and efficient method for the synthesis of the medicinally interesting optically pure (R)-2- aminohexadecanol was developed.

A modified phase-transfer catalysed enantioselective epoxidation of estra-Δ5(10),9(11)-diene, an important intermediate of anti-early pregnancy drug mifepristone 1, have been determined and investigated. Eight chiral ammonium salts (PTC A-H), used as phase-transfer catalysts, have been synthesized from cinchona alkaloids. Among them, PTC G and PTC H have exhibited satisfying catalytic activity to improve the ratio of α/β epoxide up to 7:1.

Immobilized protease-catalyzed synthesis of peptides from natural amino acids has been achieved in ionic liquids (ILs). Three ionic liquids BMIM.PF6, BMIM.BF4 and EtPy.BF4 have been tested; an effective yet simple and practical method has been devised. The product yields are comparable with those seen in molecular solvents. A max yield of 49 % for Boc-Leu-TrpOEt has been obtained. This study shows that the advantages seen in organic solvents can also be achieved in ILs, and use of such medium could provide a viable alternative to organic and aqueous media for biocatalysis.

An efficient and rapid procedure for synthesizing triarylpyridine compounds under mild reaction conditions has been described. Meanwhile, the crystal structure of 2,4,6-tris(4'-chlorophenyl)pyridine was obtained and determined by X-ray single-crystal diffraction. The procedure is operationally simple, giving good to high product yields.

The bis(β-diketone) compounds, 3,3'-(pyridine-2,6-diyl)bis(1-phenylpropane-1,3-dione) monohydrated (1a H2O) and 3,3'-(pyridine-2,6-diyl)bis(1-(pyridin-2-yl)propane-1,3-dione) monohydrated (1b H2O) were prepared by Claisen condensation of the appropriate ketone and dimethyl pyridine-2,6-dicarboxylate ester. Compounds 2,6-bis(5- phenyl-1H-pyrazol-3-yl)pyridine dihydrated (2a 2H2O) and 2,6-bis(5-(pyridin-2-yl)-1H-pyrazol-3-yl)pyridine monohydrated (2b H2O) were synthesized by reaction of the appropriate bis(β-diketone) compounds and hydrazine monohydrate.

4-(N',N'-diphenylhydrazino)-3,5-dinitrobenzoic acid in reaction with 4-hydroxy-tempo, 4-aminobenzo-15- crown-5, and 1-bromoacetyl-pyrene, yielded the corresponding esters or amides, as yellow compounds. These hydrazines, by oxidation with lead dioxide, converted into the stable hydrazyl free radicals, with a purple-violet color. Same yellow hydrazines in reaction with alkali bases are converted into the corresponding salt of green color. The newly synthesized compounds were characterized by elemental analysis, IR, UV-Vis, 1H- and 13C-NMR, and EPR (where applicable). Acidbase, redox, fluorescence and complexation properties were also studied and discussed.