Letters in Organic Chemistry - Volume 12, Issue 9, 2015

A series of thienylchalcones with fluoro and trifluoromethyl derivatives were synthesized and evaluated for their capability to inhibit human monoamine oxidase A and B. The chemical structures of the compounds have been ascertained by means of their 1HNMR, 13CNMR, mass spectroscopic data and elemental analysis. The results documented that these compounds revealed moderate to good inhibitory activities towards MAO-B than MAO-A. The most active compound, (2E)-1-(thiophen-2-yl)-3-[4-(trifluoromethyl) phenyl] prop-2-en-1-one exhibited with Ki value for MAO-B of 0.90 ± 0.05 µM with a 5-fold selectivity for MAO-B over the MAO-A isoform. All the fluorinated thienylchalcones under the present study showed as reversible inhibitors, while kinetic analysis revealed a competitive mode of binding. Molecular docking studies were executed to further explain the in vitro results of the new compounds, and to establish the hypothetical binding poses for the compounds inside the inhibitor binding cavity of hMAO-B.

The synthesis of steroid-benzenacyclononaphanone was performed using some chemical tools. In the first stage, an indol-pregnenolone derivative (3) was prepared by the reaction of pregnenolone with phenylhydrazine. Additionally, the compound 3 was bound to ethylenediamine to form a new indol-pregnenolone derivative (4). The third stage was achieved by synthesis of a benzamide derivative (6) by the reaction of 4 with 3,5-dinitrobenzoic acid using boric acid as catalyst. Finally, an ether group involved in the steroid-benzenacyclononaphanone derivative (7) was developed using the compound 6 in presence of dimetyhyl sulfoxide at mild conditions. The chemical structure of steroid derivatives was confirmed by NMR spectroscopic data. On the other hand, some physicochemical parameters of compounds 3, 4, 6 and 7 (logp, π,Rm,Vm P0 Ir and St) were analyzed. The results showed that value of logP was greater for 7 as compared to compounds 3, 4 and 6; this phenomenon is translated at a higher of lipophilicity degree. Additionally, the values of Rmand Vm were heigher for compound 7 which may have heigher steric impediment in some biological systems in comparison with compounds 3, 4 and 6. Furthermore, the values of Rm and Vm were higher for compound 7 which could result in some steric hindrance in greater biological systems as compared to compounds 3, 4 and 6.

Enantiospecific and enantioselective approaches to the natural (16R,19R)- and the unnatural (16S,19S)- THF core of the bioactive acetogenin annonacin are described which utilizes both a chiral pool synthesis and enzymatic transformations. In the antipodal (2S,5S) THF series derived from D- (+)-glucosamine, the semi-protected THF aldehyde synthon allows for two-directional synthetic elaboration through a Henry reaction with a lipid-like nitroalkane. The resulting nitroalcohol having the unnatural (2S,5S)-THF core was oxidized to the corresponding α-nitroketone using a modified Collins oxidation. The intermediate α-nitroketone has potential for the preparation of the C15-C32 core and analogues through subsequent removal of the nitro group and reduction of the carbonyl.

A new series of 1,2-disubstituted 4-phenylurazoles have been synthesized with aza-Michael addition of 4-phenylurazole and different acrylic esters. It was found that, without basic media, no reaction took place and the reactions proceeded easily in tetrabutylammonium bromide (TBAB), an ionic organic salt, under solvent-free conditions. The reactions were performed efficiently using 1,4- diaza-bicyclo[2,2,2]octane (DABCO), as an inexpensive base, at 60°C and produced the desired Michael adducts in good yields within 30-40 min. Surprisingly, no mono-Michael adducts were produced and bis-michael adducts were the only products of the reactions.

Acyl / sulfonyl hydrazines were synthesized in a one-pot reaction from carboxylic acid/aryl sulfonic acid in the presence of 1,1-carbonyl diimidazole (CDI) under ultrasound as well as under conventional heating. The reaction was performed on diverse organic molecules including simple benzoic acid (1), electron-donating and electron-withdrawing substituted benzoic acids, biologically active compounds like coumarin-3-carboxylic acid (12), 7-hydroxycoumarin-4-acetic acid (13), and therapeutic drugs like ibuprofen (14), flurbiprofen (15), naproxen (16) or tricyclic adamantane carboxylic acid (17). Benzene sulfonic acid (18) and its derivatives (19, 20, 21 and 22) were used to prepare corresponding sulfonyl hydrazide. All products were synthesized in very good yield via ultrasonic irradiation method and characterized by spectroscopic techniques including EIMS, 1H NMR, 13C NMR, IR. The method was found very simple, facile, efficient and high yielding (>90).

Potassium fluoride-clinoptilolite, which is prepared from commercially available and cheap starting materials, was used as an efficient and recyclable catalyst for Knoevenagel condensation of aromatic aldehydes with active methylene compounds under ultrasound irradiation. Short reaction times, high yields of products, ease of recovery and catalyst reusability make this new method economic and efficient.

One-pot three component reaction of various types of aldehydes, dimedone, ammonium acetate and active methylene compounds was carried out in the presence of MCM-41 functionalized with B-F bonds nanostructured catalyst for the synthesis of polyhydroquinolines. MCM-41 was prepared by Sol-Gel method under mild conditions and B-F functionalized MCM-41 with various loading amounts of boron/fluoride were prepared and characterized by XRD, SEM, FT-IR, TEM and BET techniques. The results show that B-F functionalized MCM-41 with calcination temperature of 400ºC has the best catalytic activity. The catalyst is reusable many times with moderate decrease in activity.

13C and 15N isotope labeled precursors and 6-amino-2,3-dimethylpyrimido[4,5-e][1,2,4] triazine-8-one were synthesized for the mechanistic study of dihydropteridine reductase (DHPR). Structures of precursors and the inhibitors were confirmed by UV/Vis, 13C NMR, and ESI-MS measurements.

An optically active poly(hydrazide-imide) (PHI) containing L-lysine was prepared by interfacial polycondensation. The corresponding polymeric nanocomposites have been prepared using multi-walled carbon nanotube (MWCNT) through sonication. Crystallization was studied by DSC (Differential scanning calorimetry) technique. Incorporation of nanotubes into the polymeric matrix improved the mechanical properties of the PHIMWCNT nanocomposites. Electrical percolation was observed at more than 0.5 wt% of MWCNT in the PHI matrix. All studies revealed that ultrasound assisted method causes effective dispersion of MWCNTs in the PHI matrix. The polymeric nanocomposites were characterized by FT-IR, XRD, TEM, DSC, mechanical tests, and the DC electrical conductivity measurements.

This paper focuses on the synthesis of a wide variety of di benzo spiro bis-crown compounds, in good yields using di-phenols, mono tosylates of oligoethylene glycols and caesium carbonate in acetonitrile.

New quaternary alkylammonium conjugates of steroids were obtained by two step reaction of methyl esters of bile acids with bromoacetic acid bromide, followed by bimolecular nucleophilic substitution with a long chain tertiary alkylamine. The structures of products were confirmed by spectroscopic (1H-NMR, 13C-NMR, and FT-IR) analysis, mass spectrometry (ESI-MS) as well as PM5 semiempirical methods. The biological activity of the synthesized compounds has been estimated on the basis of Prediction of Activity Spectra for Substances (PASS).