Letters in Organic Chemistry - Volume 11, Issue 9, 2014

Two new ligands with acyclic or macrocyclic structure were prepared from (R,R)-cyclohexane-1,2-diamine, the former by condensation with 5-[1-methyl-1-(1H-pyrrol-2-yl)ethyl]-1H-pyrrole-2-carboxaldehyde, and the latter by double condensation with 5,5'-(1H-pyrrole-2,5-diyl)bis(furan-2-carboxaldehyde). Subsequent reduction of the intermediate diimine and tetraimine with sodium borohydride afforded the corresponding amines, which were tested as ligands in the Henry reaction of benzaldehyde with nitromethane. The results were compared with those obtained by analogous acyclic and macrocyclic ligands and enabled to assess that the macrocyclic structure of pyrrole-containing ligand was beneficial for achieving high enantioselectivity. Moreover, it was confirmed that the asymmetric induction of ligands containing the pyrrole ring, even if a furan ring is also present, is opposite to that displayed by analogous furan- and thiophenecontaining ligands with the same chirality of the cyclohexane-1,2-diamine moiety.

A new secoeudesmanolide, named chloranerectuslactone V (1), along with three known compounds, chloranthalactone B (2), 9-hydroxy-heterogorgiolide (3), and β-sitosterol (4) have been isolated from the n-hexane fraction of the methanol extract of the leaves of Chloranthus erectus. Their structures were determined by spectroscopic analysis including MS and 2D NMR.

A convenient and efficient one-pot synthesis of 2-thioxo-dihydropyrimidine derivatives bearing piperidinylamide moiety is described. The reactions were carried out in 81-91% yields via the condensation of 1-(piperidin-1- yl)butane-1,3-dione with aromatic aldehyde and thiourea in ethanol catalyzed by p-toluenesulfonic acid at room temperature under ultrasound irradiation. The advantages of this methodology are convenient operation, mild conditions, short reaction times and high yields.

The pyrido[2,3-b]pyrazine core structure can be found in several molecules that express biological activity. We have previously published a series of these compounds that showed erlotinib-resistant tumor inhibitor potential. The common way of their synthesis is the condensation of pyridinediamines and α-oxocarbonyl compounds. If the starting dioxo compound is unsymmetrical, two regioisomers can be formed, which can display significantly different biological activity. To study the regioselectivity of this reaction we chose a model reaction and examined the impact of the reaction temperature, the acidic or basic catalysis, the amount of starting materials or the usage of dehydrating agent on the outcome of the reaction. In summary, increased regioselectivity could be observed at low temperature in acidic solvents (e.g. acetic or trifluoroacetic acid). As a result, we were able to optimize the reaction conditions to increase the amount of the biologically more active isomer. The isomers were separated, characterized by their NMR spectra and HPLC retention values, and identified by single-crystal X-ray diffraction crystallography.

The new aromaticity index based on the energy of π orbitals D = {[π1 +Σ2 n (π1 – πn )]0 /[π1 +Σ&2 n (π1 – πn)]} × a , where n are the number of occupied πorbitals and a is the number of cycles in the molecule, was used in the calculation of the aromatic character of substituted pentaatomic heterocyclic compounds. Calculations have been performed on aromatic and heteroaromatic compounds by using DFT method at B3LYP/6-311+G(d,p) level. The D values were compared with those obtained performing the calculation of Aromatic Stabilization Energy (ASE) and Isomerization Stabilization Energy (ISE) of the same compounds. In all the cases, a good correlation has been found.

A selected set of new N 1- (6-fluoro-4-oxoquinolin-8-yl)amidrazone-3-carboxylates (8a_e) incorporating Npiperazines and related congeners has been synthesized by reacting the hydrazonoyl chloride, derived from 8-amino-6- fluoro-4-oxoquinloine-3-carboxylate, with the appropriate sec-cyclic amine. Their suggested structures are supported by elemental analysis, 1H NMR, 13C NMR and ESI-HRMS spectral data. These novel compounds (8a_e) were screened for their antitumor and antibacterial activity. While no significant antitumor activity was observed, compounds 8a, 8b and 8d have shown moderate in vitro antibacterial activity against Gram positive bacteria cells. Unlike the others, compound 8a has also shown to moderately inhibit the growth of Gram negative bacteria.

We have investigated the catalytic activities of a cobalt(II) complex, [CoCl2(η2-P,P-DPEphos)](1), and an iron(III) complex, [FeCl3(η1-P-DPEphos)(η2-P,P-DPEphos)](2), [DPEphos = bis[2-(diphenylphosphino)-phenyl]ether] for alcohol oxidation reaction. Under the same set of experimental conditions, the iron complex 2 exhibits superior results over its cobalt counterpart 1. With the iron complex 2, a broad range of alcohols including benzyl alcohols, cinnamyl alcohol, aliphatic alcohol, etc. are efficiently oxidized to corresponding aldehydes or ketones using H2O2 as oxidant, at a low loading of catalyst (0.2 mol %), in a base free environment.

The novel total synthesis of icaritin (1), naturally occurring with important bioactive 8-prenylflavonoid, was performed via a reaction sequence of 8 steps including Baker-Venkataraman reaction, chemoselective benzyl or methoxymethyl protection, dimethyldioxirane (DMDO) oxidation, O-prenylation, Claisen rearrangement and deprotection, starting from 2,4,6-trihydroxyacetophenone and 4-hydroxybenzoic acid in overall yields of 23%. The key step was Claisen rearrangement under microwave irradiation. MS, 1H and 13C NMR techniques have been used to confirm the structures of all synthetic compounds.

Catalytic amount of ZnCl2 efficiently promoted rapid synthesis of arylmethylene bis(3-hydroxy-2-cyclohexene- 1-one) in water at room temperature in excellent yield. At elevated temperature, ZnCl2 also catalyzed one-pot synthesis of 1,8-dioxo-octahydroxanthene and 1,8-dioxo-decahydroacridine derivatives in good yield. In specific instances, unusual dissociation of dimedone from the arylmethylene bis(3-hydroxy-2-cyclohexene-1-one) was identified in the reaction medium. It was minimized/avoided by the addition of known excess dimedone to the reaction mixture in the one-pot synthesis of 1,8-dioxo-octahydroxanthene

Environmental friendly multicomponent protocol for the preparation of α-amino nitriles has been developed. In this methodology, glycerol was demonstrated as an efficient and alternative solvent for organic synthesis. After the reaction, glycerol was recovered and reused for further reactions. All the reactions were carried out at room temperature without using catalyst and the products were characterized by their spectroscopy analysis.

A new series of 3-hydroxyquinoline derivatives 2a-c has been synthesized by decarboxylation of corresponding quinoline-4-carboxylic acid derivatives 1a-c. These 3-hydroxyquinolines have been subjected to a number of electrophilic aromatic substitution reactions (SEAr) at C4 to obtain the target structures; 3, 4, 7, 8 and 10 through: bromination, formylation, Mannich reaction, coupling with diazonium salt and acylation, respectively. In addition, formation of fused pyrano[2,3-c]quinolin-3-one 5 and chalcone 11 were done. Trials for formation of chalcone analogue 6 were failed indicating 100% of 3-hydroxy tautomer of 2a-c. All the obtained compounds can act as good chelators and contain at least 3 H-bond acceptor groups. All compounds were evaluated for antioxidant activity by ABTS assay.

A series of novel N4-substituted 2-(trifluoromethyl)-tetrahydrobenzothieno[2,3-d]pyrimidine derivatives were synthesized by a facile three-step procedure that presented such advantages as easily accessible starting materials, mild reaction conditions, simple protocol and good overall yields. The structures of the title compounds were confirmed by IR, 1H NMR, 13C NMR, EI-MS, elemental analysis, and single-crystal X-ray diffraction.