Letters in Organic Chemistry - Volume 16, Issue 10, 2019

Biscarbonylmethylenetriphenylphosphoranes are versatile compounds derived from stabilized α-carbonylmethylenetriphenylphosphoranes, mainly prepared by transylidation or by analogue methodologies; other procedures include electrochemical oxidation, palladium-catalized insertions and displacements reactions with tellurol esters, as well as the use of Bestmann’s ylide with different reagents and reaction conditions. These biscarbonylmethylenetriphenylphosphoranes are usually converted into acetylenes by thermal treatments. Biscarbonylmethylenetriphenylphosphoranes and their oxidation products -vicinal tricarbonyl compounds- are of high importance due to their use as synthons of more complex molecules and their promising biological activity.

The selective functionalization of unactivated C(sp3)-H bonds has been regarded as an efficient and atom-economical approach for the formation of carbon-carbon or carbon-heteroatom bonds in modern organic synthesis. Especially, the oxidative activation of C(sp3)–H bonds adjacent to a heteroatom exhibits quite significant features in synthetic chemistry. For example, the direct functionalizations of amines, amides and ethers present important alternative tactics for the synthesis of various novel and useful molecules from simple starting materials. Many remarkable achievements in the area had continuously been made in the past decades. Here we reviewed recent investigations on the transformations of C(sp3)-H bond adjacent to a heteroatom.

4-Methylenepiperidine hydrochloride 1 is a key intermediate for synthesis of the novel antifungal drug efinaconazole 2. In this work, a simple and robust process has been developed to synthesize 4-methylenepiperidine hydrochloride 1, with a high overall yield of 99.1% at a high purity of 99.7% in a large-scale. Moreover, this synthetic process avoided the uses of organolithium reagent and column chromatography process which are not desirable for industrial production.

The synthesis of a novel series of 1,3,5-trisubstitiuted pyrazoline was achieved by refluxing chalcone derivative with different heteroaryl hydrazines. The newly synthesized compounds were characterized by 1H NMR, 13CNMR, mass spectral and elemental analysis data. The synthetic series of novel pyrazoline hybrids was screened for in vitro schizont maturation assay against chloroquine sensitive 3D7 strain of Plasmodium falciparum. Most of the compounds showed promising in vitro antimalarial activity against CQ sensitive strain. The preliminary structure-activity relationship study showed that quinoline substituted analog at position N-1 showed maximum activity followed by benzothiazole substitution, while phenyl substitution lowers the antimalarial activity. The observed activity was persistent by the docking study on P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction.

A series of new bisarylidene Meldrum’s acid derivatives (3a-i) were prepared in high yield by a condensation reaction between Meldrum's acid and ether functionalized dibenzaldehyde, without any catalyst. Regardless of the nature of the substitution, all the reactions were completed within 2-3 hours in ethanol at reflux condition. In the reactions, the column purification of the products was not needed. The FT-IR, 1H-NMR, 13C-NMR and mass spectra confirm the structure of the products. Furthermore, the antibacterial activities of some synthesized compounds were investigated. According to the results, these compounds showed good activities against Staphylococcus aureus, Bacillus cereus, E. coli and Pseudomonas aeruginosa.

Some new 1,3,4-thiadiazole compounds derived from 3,4-(methylenedioxy)cinnamic acid were synthesized in this study. Their structures were determined using UV-Vis, IR, 1H-NMR, and 13C-NMR spectroscopy. Moreover, the antibacterial activities of the new 1,3,4-thiadiazole derivatives were tested against Gram positive (Enterococcus durans, Bacillus subtilis, and Staphylococcus aureus) and gram negative (Salmonella typhimurium, Escherichia coli, Salmonella enteritidis, Salmonella infantis, Salmonella kentucky, Enterobacter aerogenes) bacteria using the disk diffusion method. Furthermore, their antifungal activity was tested against Candida albicans using the disk diffusion method. Some of the synthesized compounds (V, VII, XIII, and XIV) showed antibacterial activity against S. aureus. Also, one synthesized compound (VIII) showed antibacterial activity against E. coli, exhibiting 8 and 9 mm inhibition zones using 50 and 80 μL. One compound (IX) showed antibacterial activity against E. aerogenes, exhibiting a 12 mm inhibition zone using 80 μL. One compound (XIII) showed antibacterial activity against S. kentucky, exhibiting an inhibition zone of about 9 mm using 80 μL. Also, one compound (VII) showed antibacterial activity against E. durans, exhibiting 7, 7, and 8 mm inhibition zones using 30, 50, and 80 μL. None of the compounds (I-XV) showed antifungal activity against C. albicans. These results showed that some of the synthesized compounds could be used as antibacterial agents.

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

A multicomponent one-pot atom-economic reaction is performed for an efficient synthesis of 1-amidoalkyl-2-naphthol from aromatic aldehydes, β-naphthol and amide/urea promoted by hexachlorocyclotriphosphazene (HCCP). Various techniques such as stirring, microwave irradiation and thermal technique (hot plate and oil bath) were used in different solvents for the synthesis of 1- amidoalkyl-2-naphthol derivatives with moderate to excellent yield. Among the four methods, microwave irradiation and oil bath heating provide high yield as compared to the hot plate heating and stirring method. The low yield may be due to the formation of undesired side-products due to non-uniform heating.