Sixteen novel thiazolidinedione (TZD) and rhodanine (RD) derivatives were designed and synthesized by introducing a pyrimidine moiety at different sites of pioglitazone's structure. The effects of synthesized compounds on regulating glucose metabolism, improving insulin sensitivity, and activating the peroxisome proliferator-activated γ receptor (PPAR-γ) were evaluated in βTC6 cells. Compounds TZDs # 7a, 7b, 7c, and 29 reduced the basal insulin secretion by ∼20.0-67.0% and increased insulin secretion stimulated by glucose by ∼25.0-50.0% compared to control. Compounds TZDs # 14 and 21 and RDs # 33a-b and 33d-f increased basal insulin secretion by ∼20.0-100.0%, while its glucose-stimulated secretion remained unchanged. These findings suggested that the former compounds can act as antihypoglycemic during fasting and antihyperglycemic during postprandial conditions. The latter compounds should be administered before meals to avoid their hypoglycemic effect. Additionally, both TZDs and RDs improved insulin sensitivity by increasing glucose uptake by 17.0-155.0% relative to control. In silico molecular docking of synthesized drugs onto the PPAR-γ structure revealed exothermic binding modes through hydrogen bonding, van der Waals forces, and π-π stacking with binding affinities of -6.02 to -9.70 kcal/mol. Insights into the structure-activity relationship revealed that the introduction of pyrimidine linked to sulfonyl or peptide groups accounted for increased antidiabetic activity. These results demonstrated novel TZDs and RDs with high potency in stimulating insulin secretion, enhancing insulin sensitivity, and activating PPAR-γ relative to pioglitazone. They are recommended for further development as potential antidiabetic agents.

The construction of 2,2-disubstituted indolines has long presented a synthetic challenge without any general solutions. Herein, we report a robust protocol for the dearomative Meerwein-Eschenmoser-Claisen rearrangement of 3-indolyl alcohols that provides efficient access to 2-substituted and 2,2-disubstituted indolines. These versatile subunits are useful for natural product synthesis and medicinal chemistry. The title [3,3] sigmatropic rearrangement proceeds in generally excellent yield and transfers the C3-indolic alcohol chirality to the C2 position with high fidelity, thus providing a reliable method for the construction of enantioenriched 2,2-disubstituted indolines. The power of this methodology is demonstrated through the concise and strategically unique total synthesis of the marine natural product hinckdentine A, which features a dearomative Claisen rearrangement, a diastereocontrolled hydrogenation of the alkene product, a one-pot amide-to-oxime conversion using Vaska's complex, and a regioselective late-stage tribromination.

In this paper, a selective synthesis of indolo[1,2-c]quinazolines and indolo[3,2-c]quinolines through the cascade reactions of 2-(1H-indol-2-yl)anilines with sulfoxonium ylides is presented. The formation of products involves the generation of a carbene species from sulfoxonium ylide and its N-H bond insertion reaction with 2-(1H-indol-2-yl)aniline followed by deoxygenative imine formation, intramolecular N- or C- nucleophilic addition and deoxygenative aromatization. This switchable synthesis was condition-dependent. In the presence of K₂CO₃ in CH₃CN, the reaction mainly furnished indolo[1,2-c]quinazolines. In the presence of HOAc in dioxane, it selectively afforded indolo[3,2-c]quinolines. In addition, direct C-H/N-H functionalization of the products obtained provides a convenient and direct access to polycyclic heteroaromatic compounds. These novel protocols have advantages such as readily accessible substrates, easily tunable selectivity, good compatibility with diverse functional groups, and the use of air as a cost-free and sustainable oxidant.

An efficient strategy for the synthesis of 6-unsubstituted indolo[1,2-c]quinazolines is described. The Pd-catalyzed reaction of o-(o-aminophenylethynyl) trifluoroacetanilides with Ar-B(OH)2 afforded 2-(o-aminophenyl)-3-arylindoles, that were converted to 12-arylindolo[1,2-c]quinazolines by adding dimethylformamide dimethyl acetal (DMFDMA) to the reaction mixture after extractive work-up. This reaction outcome is different from the previously reported Pd-catalyzed sequential reaction of the same substrates with Ar-I, Ar-Br and ArN2+BF4-, that afforded 12-arylindolo[1,2-c]quinazolin-6(5H)-ones. Moreover, 12-unsubstituted indolo[1,2-c]quinazolines can be obtained both by reacting 2-(o-aminophenyl)indoles with DMFDMA or by sequential Pd-catalyzed reaction of o-(o-aminophenylethynyl)aniline with DMFDMA.

A novel heteroannulation reaction between α-amino imides and in situ generated arynes has been developed for the synthesis of 2,2-disubstituted indolin-3-ones. An enantioselective total synthesis of the marine alkaloid (+)-hinckdentine A was subsequently accomplished using this reaction as a key step. A catalytic enantioselective Michael addition of an α-aryl-α-isocyanoacetate to phenyl vinyl selenone was employed for the construction of the enantioenriched α-quaternary α-amino ester.

A simple and practical procedure for the selective preparation of 3 H-indol-3-one and indolo[1,2- c]quinazoline derivatives through copper-catalyzed aerobic oxygenation and intramolecular cyclization reactions of 2-(2-amidoaryl)-1 H-indoles in the presence of acid has been disclosed. Interestingly, the reaction outcomes are exclusively dependent on the reaction medium employed. With DMF as the solvent, the amide moiety of indole substrates could act as an auxiliary to enable the indole's oxygenation reaction with molecular oxygen from air as the oxidant to give 3 H-indol-3-one derivatives in a highly selective manner. On the other hand, when the reactions were performed in 1,4-dioxane, the amide moiety switched to participate in an intramolecular indolyl N1-cyclization to afford indolo[1,2- c]quinazolines as the predominating products.

A few pyrene-based fluorescent compounds were synthesized using Pd/Cu-catalyzed cross-coupling reaction. Photophysical properties of the π-conjugated pyrene derivatives were studied and the results indicate materials with high quantum efficiency and high extinction coefficient. No π stacking was observed in the crystal lattice. The molecules described here may be useful in developing sensors or imaging agents.