Letters in Organic Chemistry - Volume 12, Issue 7, 2015

A tandem metal-free synthesis of partly and fully substituted pyrimidines has been accomplished from α,β-unsaturated ketones and benzamidine in presence of triethyl amine. The reaction proceeds via [3+3] annulation-oxidation sequence and the protocol has been found successful for the synthesis of a wide range of pyrimidine derivatives.

Though L-dopa is an effective drug for Parkinson’s disease, the usage of L-dopa in clinical treatment is limited for its physico-chemical properties which affect the bioavailability of L-dopa and increase the side effects of L-dopa. For improving the availability of L-dopa, L-dopa-L-His was synthesized by Fmoc solid-phase peptide synthesis, purified by reversed-phase HPLC and characterized by using 1H, 13C NMR and ESI-MS. The interaction of L-dopa-L-His and L-dopa with ctDNA has been investigated respectively by UV absorption and fluorescence spectroscopy. The results indicated that both L-dopa and L-dopa-L-His interacted with ctDNA through intercalative mode. The binding constant of L-dopa and Ldopa- L-His with ctDNA were 4.99x1010 L·mol-1·s-1 and 8.25x1011 L·mol-1·s-1, which showed a higher affinity of L-dopa- L-His to DNA for the imidazole side-chain. Meanwhile, compared with the free L-dopa, gel electrophoresis assay also demonstrated that the L-dopa-L-His interacted with plasmid DNA by stronger intercalation.

A clean, efficient and facile one-pot protocol was developed for the synthesis of a series of new 3,4-substituted coumarins (warfarin analogous compounds) by a one-pot reaction using catalytic amount of Fe3O4 nanoparticles under solvent-free conditions. This green method offers significant advantages in terms of its simplicity, low catalyst loadings, high product yields, recyclability of catalyst and non-toxic nature.

In this report, synthesis and characterization of silica perchloric acid nanosphere as a novel and heterogeneous catalyst are described. It has a spherical shape and the particle size is between 75 and 100 nm. The catalytic activity has been investigated in coupling reaction involving a variety of aldehydes, phthalhydrazide, dimedone at 80°C under solvent-free conditions. This method offers advantages such as good yields, simple conditions, shorter reaction time, and reusable activity catalyst.

Two efficient synthetic routes to (S,S)-ethambutol, a first line drug used for tuberculosis treatment, based on the chiral pool approach viewing L-methionine as a starting material are reported. Several advantages over the traditional synthetic routes were observed: simple, safe, inexpensive reagents, and minimum byproduct formation. The key intermediate (S)-(+)-2-amino-1-butanol was obtained in its enantiomerically pure form from the corresponding aminobutyric acid.

The aromaticity index D, usually obtained by using DFT/B3LYP/6-311G+(d,p) theoretical method, was tested using different basis sets: aug-cc-pVDZ, aug-cc-pVTZ, aug-cc-pVQZ, LanL2DZ, LanL2MB, SDD, DGTZVP, and DGDZVP2 were used. The results showed the D values are not largely sensible to the variation of the basis set. D values were correlated to ERE and ASE. The best correlation between D and ERE was obtained by using aug-cc-pVTZ basis set. The best correlation between D and ASE was obtained by using LanL2MB in the case of monocyclic compounds, and by using 6-311G+(d,p) in the case of polycyclic compounds.

The replacement of platinum in carboplatin, oxaliplatin and nedaplatin by zinc metal (in bulk and nano-scalled) produces biologically active compounds with increased solubility in water. We compared, in this work, three synthesized zinc-complexes from the ligands of platinum-anticancer drugs. The structural characterization of the products has been determined on the basis of their atomic absorption spectroscopy, elemental analysis, FT-IR, 1H and 13C NMR spectra. The crystalline structure and morphology of the products have been shown by XRD and SEM techniques. The antibacterial activities of the complexes have been examined through the growth inhibitory zone and minimal inhibitory concentrations.

An efficient one-pot synthesis of dihydropyrano[3,2-c]quinolones 4a-p by three-component reaction of N-methylquinoline-2,4-dione (1) with malononitrile (3a) or ethylcyanoacetate (3b) and benzaldehydes 2a-h in water in the presence of TBA acetate has been described. The above synthesis was also tried alternatively by the reaction of 1 with 2a-h in refluxing water using TBA acetate for 30 min and yielded 5. Compound 5 on reaction with 3a or 3b did not yield the target compound 4. This was approached alternatively by the reaction of 2a-h with 3a or 3b that gave benzylidine derivatives 6a-h which on further reaction with 1 gave the title compound 4a-p. The methodology described here has the advantages of environment friendliness, higher yields, shorter cost, low reaction times and convenient operation.

A rigid shape-persistent fluorescent macrocycle PhenMac was synthesized using Sonogashira coupling reaction and TIPS-decoupling in a single pot. 2,9-dichloro-1,10-phenanthroline was reacted with TIPS-protected diyne 2 in the presence of Pd(PPh3)2Cl2, CuI and TBAF at 100 °C. PhenMac was obtained as yellow fluorescent compound; characterized by NMR, ESI, MALDI-TOF, CHN, IR and UVvisible spectroscopy. In chloroform, PhenMac showed λex-max at 331 nm while λem-max was observed at 407 nm. Under UV light, PhenMac showed more fluorescence in CHCl3, ethanol, and DMF while the fluorescence was quenched in triethylamine. PhenMac will be used in various applications of [poly]catenanes, supramolecular chemistry and nanotechnology.

Reaction of triphenylmethanol with acetylacetone in 1,2-dichloroethane medium in the presence of Cu(OTf)2 or Al(OTf)3 catalysts resulted in 3-(9-phenyl-9H-fluorene-9-yl)-pentanedione- 2,4 with 25% yield. 3-(9-Phenyl-9H-fluorene-9-yl)-pentanedione-2,4 was also obtained by an alternative synthesis between 9-phenylfluorene-9-ol and acetylacetone in the presence of Al(OTf)3 catalyst with practically quantitative yield.

The conformational behaviors of 2-fluoro-2-oxo-1,3,2- (compounds 1-3), 2-chloro-2-oxo- 1,3,2- (compounds 4-6), 2-bromo-2-oxo-1,3,2- (compounds 7-9), -dioxa, -dithia, -diselena phosphorinanes have been analyzed by means of hybrid density functional theory (B3LYP/6- 311+G**) and ab initio molecular orbital (HF/6-311+G**) based methods and NBO interpretation. The results justified the axial conformations preference of compounds 1-9. The calculated relative energies ΔE0 and Gibbs free energy difference values (ΔGeq-ax) between the axial and equatorial conformations decrease from compound 1 to compound 3, from compound 4 to compound 6 and from compound 7 to compound 9. The NBO analysis showed the same trends for the accordingly calculated Generalized Anomeric Effect (GAE) values. The correlations between the GAE, dipole-dipole interactions, Wiberg Bond Index (WBI), orbital occupancies, HOMO, LUMO energies and structural parameters for rationalization of conformational behavior of compounds 1-9 have been investigated.