Letters in Organic Chemistry - Volume 18, Issue 5, 2021

Hybrid systems containing pyrazole moiety show a wide spectrum of biological activities. To access novel hybrids with pyrazole ring, in this work we synthesized twenty pyrazole-carboxylic acids and twenty pyrazole-carboxamides, using simple synthetic methods, to be used as building blocks in the development of new structures.

We present the preparation of the new precursor 6-O-(2-tosyloxyethoxy)-6-O-desmethyl-3- O-trityl-diprenorphine (TE-TDDPN) for a one-pot, two-step nucleophilic radiosynthesis of 6-O-(2- [18F]fluoroethyl-6-O-desmethyl-diprenorphine ([18F]FE-DPN). The route to the precursor consists of a five-step synthesis starting from diprenorphine. We also provide alternative synthesis routes for the cold reference standard and the complete 1H- and 13C-NMR assignment of the prepared derivatives.

The extract of marine green algae Enteromorpha sp. was evaluated in vitro for inhibitory activity against mushroom tyrosinase enzyme. The principle active agents i.e. coumarin; 4-hydroxycoumarin (1) and two sterols; ergosta-5,7,22-trien-3β-ol (2) & ergosterol peroxide (3) were isolated for the first time, from a crude methanol extract of Enteromorpha sp. showing anti-tyrosinase activity. Their structures were elucidated by IR, extensive NMR spectroscopy, LC-ESI-MS, Single crystal X-ray diffraction techniques. Thus, Enteromorpha sp. can be an alternative edible anti-tyrosinase agent.

We straightforwardly synthesized 18 different types of palladium nanoparticles by using a series of palladium metal precursors and ionic liquids. All the materials went for XRD, TEM, and ICPOES analysis, before going to Heck cross-coupling reaction as a catalyst. We evaluated the catalytic performance of our developed IL#Pd MNP catalyst over Heck cross-coupling reaction between different terminal olefins with various 3-iodo-benzopyrones, including sterically hindered, electron-rich, electron neutral and electron-deficient systems. We obtained the Heck cross-coupling reaction product in good to average yield under phosphine free reaction condition with an added advantage of 6 times catalyst recycling.

An extended compound library of spiro[cycloalkane-pyridazinones] with a high Fsp3 character is targeted. There are two possibilities to improve the physicochemical parameters of a drug candidate molecules or building blocks, either to replace the aromatic systems with bioisoster heteroaromatic moieties, e.g. with one or two nitrogen containing ring systems (pyridines, pyridazines, pyrimidines, etc.), or to increase the Fsp3 character of the compounds. Using a new synthetic approach, the Grignard reaction of 2-oxaspiro[4.5]decane-1,3-dione and 2-oxaspiro[4.4]nonane-1,3-dione with p-halophenyl- or p-alkylphenyl-magnesium bromide resulted in the formation of the corresponding 2-oxoethyl-cycloalkanecarboxylic acids, which served as starting materials for the pyridazinones by reaction with hydrazine or phenylhydrazine. The pyridazinones obtained were alkylated with methyliodide or benzylbromide. 16 Novel 4-tolyl- or 4-halophenyl-2,3-diazaspiro[5.5]undec-3-en-1-one and 4-tolyl- or 4-halopyhenyl-7,8-diazaspiro[4.5]dec-8-en-6-one, and their N-methyl, N-benzyl, and N-phenyl derivatives were synthetized. The physicochemical parameters and the Fsp3 character of the novel compounds obtained were studied. A few of them showed excellent logP and clogP values, but the introduction of a further phenyl group seemed to be disadvantageous.

Environmentally benign syntheses of One-pot sequential reactions of benzoyl chloride with amines followed by the treatment of molecular I2 reagent under basic conditions provide benzoyl tetrazoles and guanidines in moderate to excellent yields. This one-pot synthesis has several advantages such as mild reaction conditions, short reaction time, convenient workup, high yields, using cheap and readily available reagent molecular Iodine. In addition, functional group tolerance has been explored.

A nucleophilic aromatic substitution via a new and facile cesium fluoride catalyzed synthetic approach to get 5-aryloxy-1-phenyl-1H-tetrazoles was developed. Dual usage of cesium fluoride as a nucleophilic catalyst as well as an electrophilic catalyst afforded the desired products at room temperature in a short reaction time without purification in high yields. This simple but useful reaction may be a rapid and reliable strategy for the synthesis of tetrazolyl ethers.

A Lewis acid BF3•Et2O-mediated intramolecular cycloaddition reaction of mahanimbine (1) is described. Three cycloadducts, bicyclomahanimbine (2), cyclomahanimbine (3) and murrayazolinine (4) were obtained. The structural characterization of these compounds was determined by 1D and 2D NMR experiments. These compounds showed no cytotoxic activity against human MRC-5 cells (IC50 > 60 μg/mL). Compound 3 showed the highest inhibition cytotoxic effects against HeLa and HL-60 cancer cells with IC50 values of 10.0 and 28.7 μg/mL, respectively. This strategy opens a new approach for the synthesis of biologically significant cyclic monoterpenoid pyrano[3,2-a]carbazole alkaloids.

Solvent free synthesis of dihydropyrano[3,2-b]chromenediones was formulated via multicomponent reactions of kojic acid, dimedone and several substituted aromatic aldehydes catalyzed with BCl3. Reactions progressed efficiently and the corresponding heterocyclic products were obtained in good to high yields within short period. The developed protocol is one of the better and efficient alternative methods for the synthesis of dihydropyrano[3,2-b]chromenediones. The simple reaction procedure, easy separation of products, radially available catalyst are certain benefits of this reported protocol.

Phthalhydrazide immobilized on TiO2-coated nano Fe3O4 (Fe3O4-P) was synthesized and characterized by FT-IR, XRD, SEM, EDS and VSM analysis. The resulting magnetic nanocatalyst was used as a catalyst for the synthesis of chalcone derivatives which affords the desired products in good to excellent yields. This catalyst can be isolated readily after completion of the reaction by an external magnetite field and reused several times without significant loss of activity.

Four eugenol metabolites were concisely synthesized and their structures were confirmed by ¹H-NMR, ¹³C-NMR and high-resolution mass (HR-MS). Among them, the synthesis of eugenol-β-Dglucuronide (3) and eugenol sulfate (4) was reported for the first time. The successful synthesis of the four eugenol metabolites provides a material basis for further metabolic study of prodrug aspirin eugenol ester (AEE).