Letters in Organic Chemistry - Volume 17, Issue 9, 2020

The ortho effect arises in certain electrophilic aromatic substitutions when a meta director is meta to an ortho/para director. Among the three expected isomer products, only the two isomers ortho to the meta director are produced normally. To find an explanation for the ortho effect, nitrations of two properly substituted benzenes were explored. Evidence supported an explanation based on resonance involving the meta director.

Thiazolidine-2, 4-diones and their derivatives are a well-established chemical class of compounds that express their pharmacological actions through insulin sensitization and enhanced glucose utilization in peripheral tissues. In the current research different approaches have been employed to synthesize thiazolidine-2, 4-dione derivatives and these synthesized compounds were chemically characterized for the establishment of their chemical structures. A series of thiazolidine-2, 4-dione (TZD) derivatives, Scheme 1 (3A-3V) 22 compounds, were synthesized and characterized by FT-IR, 1H NMR and mass spectral analysis. The title compounds were screened for their in vitro and in vivo antidiabetic, antioxidant, and cytotoxicity studies. In vivo antihyperglycemic effect was assessed by measuring plasma glucose (PG) levels in alloxan-induced type II diabetic rat models. The synthesized TZD derivatives were evaluated for hepatotoxicity and pancreatic tissue integrity. Antioxidant activity was evaluated by the DPPH method and H2O2 method. Thiazolidinedione derivatives were subjected to predict free energy of binding towards target PPARγ, using rosiglitazone as the reference compound for molecular docking visualization through the FlexX docking program. Molecular docking studies are also performed for understanding the binding of a ligand to a receptor. The compound 3V 4-(5- (naphthalen-1-ylmethylene)-2, 4-dioxothiazolidin-3-yl) benzoic acid exhibited better blood glucoselowering activity than that of the standard drug rosiglitazone. Compound 3T and 3U exhibited potent antioxidant activity. Among the tested compounds for cytotoxicity using an MTT assay, compound 3H 5-(4-chlorobenzylidene)-2, 4-dioxothiazolidin-3-yl) benzoic acid exhibited better viability and cytotoxicity activity. From selected anti-diabetic targets, the proposed derivatives exhibited better interaction with PPARγ receptor, for example, while rosiglitazone showed a docking score of -19.891 kJ/mol, compound 3V exhibited highest docking score of -31.6617 kJ/mol. Computational molecular docking study demonstrated the selectivity and provided a binding model for the further refinement of this chemotype. Therefore, this series of thiazolidine-2, 4-diones derivatives (3A-3V) have considerable importance for development as a potential antihyperglycemic and hypolipidemic agents.

Phytochemical investigation of the methanolic extract of the stem bark of Casimiroa edulis afforded four coumarins. Various spectroscopic experiments were used to characterize the isolated coumarins. The structures were identified as auraptene (K-1), suberosin (K-2), 5-geranyloxypsoralen (bergamottin) (K-3), and 8-geranyloxypsoralen (K-4), based on the chemical and spectral analysis. Among these compounds, suberosin (K-2) and 5-geranyloxypsoralen (bergamottin) (K-3) were isolated for the first time from this genus, and auraptene (K-1) was isolated from this plant for the first time. Cytotoxicity of pure compound K-4 and sub-fraction MD-3 was evaluated against HeLa and T47D cell lines and moderate activity was found with an IC50 value in the range 17.4 to 72.33 μg/mL.

In this study, a new type of luminogen with aggregation-induced-emission (AIE) behavior was designed and synthesized. The result of single-crystal X-ray structure showed a planar structure in which the dihedral angle between two aromatic rings is less than 30o. Moreover, two different intermolecular hydrogen bond interactions supported the stability of the crystal structure. After the formation of organic nanoparticles in poor solubility solvent, the emission intensity of the desired product was increased and the enhancement achieved was 14-fold. This new design of luminogen provided further understanding of the AIE mechanism.

We have successfully explored the potential MoO3 nanoparticles as a heterogeneous catalyst for the cyclocondensation of hydrazines/hydrazides with 1,3-dicarbonyl compound in aqueousalcoholic medium at room temperature. The present method has been developed using green chemistry measures and offers a range of N-substituted pyrazoles with moderate to excellent yields. Utilization of non-toxic catalyst, wide substrate scope and environmentally benign reaction medium are the important features of the developed protocol. Interestingly, MoO3 nanocatalyst can easily be recovered from the reaction mixture and showed excellent reusability with a modest change in product yield. We have reported herein the synthetic pathway with less disastrous effect in the atmosphere.

A one-pot Cu-catalyzed synthesis of functionalized alkynyl imidamide by terminal alkynes, trichloroacetonitrile and aniline or benzyl amine is reported. The compounds were produced via coupling reaction of terminal alkynes with trichloroacetamidine. This method was performed under mild, ligand-free conditions and easy work-up method.

With regard to the importance of quinazoline as a privileged scaffold, herein we report the synthesis of twenty seven 2,4-disubstitute quinazoline derivatives in a new catalyst free condition. In the current work, poly ethylene glycol (PEG1000) as an inexpensive, very simple commercially available, ecofriendly and low melting point solvent was used. Air bubbling, a green oxidant, for oxidation purpose was also used. This is the first report about using PEG1000 as a solvent simultaneously with air bubbling as oxidant in quinazoline synthesis. All of the compounds 1-27 were synthesized in high yield with very simple work up and purification process without using column chromatography. All the structures were confirmed using 1H NMR, 13C NMR, IR, MS and elemental analysis.

L-Proline was covalently tethered on thermoresponsive ionic block copolymers that formed micelles in aqueous solutions. The block copolymers consisted of a poly(N-isopropylacrylamide) (PNIPAAm) segment and an anionic or cationic polymer segment. These copolymers exhibited lower critical solution temperature (LCST) behavior at ca. 35-40°C, and achieved thermal stimuli-induced formation and dissociation of micelles. The copolymer generated micelles in aqueous solution at a higher temperature, where a catalytic aldol reaction proceeded with high diastereo- and enantioselectivities. The micelles dissociated at lower temperature to form a clear solution such that the products could be efficiently extracted from the aqueous reaction mixture. Extraction of the aldol product with an organic solvent from the aqueous solution of the anionic copolymer was more efficient than from the nonionic copolymer solution.

This manuscript focuses on the reactions of 4-phosphorylated 5-hydroxyhexa-2,3-dienoates with protected or unprotected hydroxy groups involving 5-endo-trig cyclizations. Reactions with electrophiles result in mixtures of the 2,5-dihydro-1,2-oxaphosphole-5-carboxylates and the 5-phosphorylfuran- 2(5H)-ones by competitive electrophilic cyclization due to the neighboring phosphonate (phosphine oxide) and the carboxylate groups participation. 4-Phosphorylated 5-hydroxyhexa-2,3-dienoates were smoothly transformed into the corresponding 4-phosphoryl-2,5-dihydrofuran-2-carboxylates by using 5 mol % of a silver salt as a catalyst in the 5-endo-trig cycloisomerization reaction.