Irradiation of indole or isocarbostyril derivatives with allenyl side chain under appropriate conditions gave the corresponding methylenecyclobutane-fused N-heterocycles stereoselectively in high yields through intramolecular [2+2] cycloaddition. These addition products could be transformed to ring-expanded compounds without loss of the configuration by using a sequence of epoxidation and skeletal rearrangement.

An efficient and novel synthetic route of chlorfluazuron (1) on a ton scale has been developed, from the commercially available chemicals 3,5-dichloronitrobenzene, 2,3-dichloro-5-(trifluoromethyl)pyridine, and 2,6-difluorobenzamide. The key intermediate, 4-amino-2,6-dichlorophenol (2), was synthesized in one step by 3,5-dichloronitrobenzene with 78.1% yield and 99.5% purity. At the same time, 3,5-dichloroaniline (15), a co-product with great market demand, was also obtained with 20.9% yield and 99.2% purity. Chlorfluazuron (1) was obtained from 4-amino-2,6-dichlorophenol (2) in 91.9% yield over two steps and 99.2% purity. Compared with the original process route, the new synthetic route has the advantages of fewer reaction steps, higher overall yield, less process safety hazard and environmental impact.

Hexachlorocyclotriphosphazene (HCCP, N3P3Cl6, 1) was treated with anilines in THF at 0 ºC to give a corresponding mono-substituted 2-anilino-2,4,4,6,6-pentachlorocyclotriphosphazenes (N3P3Cl5(NAr(R)), 2) in good to moderate yield. Multi-substituted products N3P3Cl6-n(NAr(R))n (n ≥ 2)) were not detected in 31P NMR spectra of the reaction mixture.

The unnatural enantiomer of the alkaloid codonopsinine was prepared employing a suitably substituted alkoxyallene equipped with a D-fructose-derived auxiliary. The crucial lithiated 1-alkoxy-3-arylallene was generated in situ from easily available 1,2:4,5-di-O-isopropylidene-3-O-[3-(4-methoxyphenyl)-1,2-dien-1-yl]-β-D-fructopyranose and treated with an N-tosyl imine to afford a diastereomeric mixture of the corresponding allenyl adducts. Their cyclization with silver nitrate in acetonitrile in the presence of potassium carbonate furnished highly substituted 2,5-dihydropyrrole derivatives. After separation, straightforward synthetic operations, with highly diastereoselective hydroborations as key step, provided (+)-codonopsinine (≥95% ee) and one of its stereoisomers.

1,3-Thiazole is one of the most adaptable scaffolds for heterocyclic compounds. In recent years, thiazole has attracted focus in organic and medicinal chemistry due to its improved effectiveness and significant biological activities. Numerous reviews have reported on the synthesis and pharmacological activities of thiazoles. However, synthesis, pharmaceutical, and chemical applications have not been completely reviewed. The present review focuses on recent work on the synthesis, pharmaceutical and chemical applications of substituted thiazoles. This review discusses the most recent advancements in thiazole-based compounds and emphasizes the importance of design, drug discovery, and the use of thiazole in chemical applications. Additionally, this article is aimed to aid researchers in identifying potential future avenues for the creation of more effective thiazoles.

The 3,3'-diethynyl-substituted 2,2'-bibenzofuran derivatives 1 and 3,7-diethynyl-substituted benzodifuran derivatives 2 were prepared from 1,4-bis(2-methoxyphenyl)-1,3-butadiyne and diethynyldimethoxybenzene by iodocyclization followed by Sonogashira coupling reaction, respectively.

A new steroid, terreus steroid (1), and eight known compounds (2–9) have been isolated from the airborne-derived fungus Aspergillus terreus. The structure of terreus steroid (1) was elucidated based on the chemical/physicochemical evidence. The cell death-inducing activities of the isolated compounds with or without Adriamycin (ADR) were observed using time-lapse cell imaging. Among the isolated compounds, terreus steroid (1) and territrem B (3) significantly reduced the number of mitotic entry cells at 60 μM. In addition, terreus steroid (1), territrem C (2), territrem B (3), epi-aszonalenin A (5), and methyl 3,4,5-trimethoxy-2-(2-(nicotinamido)benzamido)benzoate (6) significantly increased the number of dead cells on Adriamycin-treated HeLa cells.

Carbazoles could be easily and rapidly synthesized in a one-pot synthesis using 4-methyl-1-cyclohexanone and p-anisidine in a continuous microwave-heated reaction (1 h, 140 °C). Eustifoline-B, a trace constituent of the roots of Murraya euchrestifolia, was synthesized using the carbazole derivative glycozoline obtained by this method. Next, nine carbazoles isolated from the leaves of M. koenigii and three synthetic carbazoles were evaluated for their antiproliferative activities against human astrocytoma U-251 MG cells [that is, non-cancer stem cells (non-CSCs)] and cancer stem cells (CSCs) isolated by sphere formation. Carbazoles with geranyl or prenyl moieties showed antiproliferative activity against U-251 MG CSCs. In particular, the synthetic compound eustifoline-B showed significant antiproliferative activity against U-251 MG CSCs (IC50 = 2.9 μM). Interestingly, eustifoline-B showed an approximately 10-fold higher antiproliferative activity against U-251 MG CSCs than against U-251 MG non-CSCs (IC50 = 29.4 μM).

Hexachlorocyclotriphosphazene (HCCP, N3P3Cl6) was treated with Li aryloxide in THF at -40 ºC to give monoaryloxypentachlorocyclotriphosphazene (N3P3Cl5(ArO)) selectively. N3P3Cl5(ArO) did not give further aryloxylated products N3P3Cl6-n(ArO)n (n ≥ 2) under the same reaction conditions. In mass spectra (MS) of N3P3Cl5(ArO), [N3P3Cl5(ArO)]+ were detected by EI method, whereas partially hydrated products [N3P3Cl4(ArO)(O-)] were detected instead of [N3P3Cl5(ArO)]+ by ESI method.

Fluorinated heterocycles are a major component of the field of modern medicinal chemistry due to the widespread presence of heterocyclic ring structures in naturally occurring biological molecules. The effect of the presence of fluorinated heterocyclic moieties on chemical properties such as intermolecular interactions and solubility can be used to impart synthetic molecules with useful, drug-like characteristics. Pyridazines, which are aromatic six-membered rings with a chemical formula (CH)4N2 and adjacent nitrogens, afford important biological activities to drug molecules by increasing their solubility and ability to complex with target molecules. Our method of synthesizing fluorinated pyridazines incorporates an SNAr reaction on 5,6-fused ring pyridazines with a variety of aryl substituents at the 1- and 4-positions with pentafluoropyridine. The target products were identified by spectroscopic characterization and confirmed via X-ray crystallography. Computational studies were also performed on the phenyl-substituted case, including the calculation of an optimized structure using PBE with a cc-pVTZ basis. This analysis found the addition of perfluorinated pyridine significantly altered the esp mapping, HOMO-LUMO, and NBOs of the modified pyridazine compared to other 5,6-fused ring heterocycles.

2,5-Bis(methoxycarbonyl)-3,4-diphenylcyclopentadienone (1a) reacts with prop-2-yn-1-ols (2) in the presence of 1,4-diazabicyclo[2.2.2]octane at room temperature to produce bicyclic carbocycles (4) in moderate yields, as well as tetracyclic carbocycle (5). The bicyclic carbocycle, which has a 3-methylenetetrahydrofuran moiety, is derived from the anionic cyclization of the 1,4-adducts of 1a and 2 onto a non-activated alkyne. The mechanism of the cascade reaction was discussed based on the density functional theory calculations and the X-ray crystallographic analysis.

6-Aminouracils are very useful intermediates for building different categories of heterocyclic compounds. 6-Aminouracils are electron rich compounds due to the presence of free amino group which can initiate interactions with electron deficient centres or activate the nearby C-5 position to start the reaction followed by cyclization in most cases. The present review summarizes the different reactions developed for the synthesis of substituted and annulated pyrimidines. A diversity of substituted pyrimidines was prepared directly from reactions of 6-aminouracils with some electrophilic reagents, meanwhile formation of fused pyrimidines were achieved by reaction of 6-aminouracils with a variety of reagents such as aromatic and aliphatic aldehydes, acyclic and cyclic methylene ketones, cyclic enols, alkynes, iminium salts and a diversity of other reagents.

An efficient one-pot, three-step procedure for the aza-Michael addition of methyl 3-iminoacrylates with secondary amines followed by intramolecular cyclization and silylation successfully afforded novel 1,2,3,5-tetrasubstituted pyrroles in high yields.

A total of eleven compounds were isolated from the ripe and dried fruits of Embelia oblongifolia Hemsl. Compound 1 was a new one named embeloside A, in addition, compounds 2-4, 6 and 10 were isolated from this genus for the first time. Their molecular structures were elucidated by 1D/2D NMR spectroscopic analysis, HR-ESI-MS spectral data and charged aerosol detector (CAD). Further, hypoglycemic activity evaluation showed that compound 1 could reduce the fasting blood glucose levels in diabetic rats. Therefore, the results suggest that compound 1 might provide a theoretical basis for the development of potential hypoglycemic drugs. The discovery of compounds 1-11 might provide experimental guidance for the further development of Embelia oblongifolia Hemsl.

Based on the chroman-4-one ROR1 inhibitor ARI-1, two new series of 4H-pyrido[1,2-a]pyrimidin-4-one derivatives were designed and synthesized, and their biological activities were investigated. In vitro biological activity assays showed that compound 10b exhibited the best antiproliferation activity against H1975 (IC50 = 0.572 μM), which was superior to the lead compound ARI-1 (IC50 = 3.51 μM). Compound 10b also dose-dependently induced G0/G1 phase block and apoptosis. In addition, 10b exhibited inhibitory activity against ROR1 and modulated the ROR1 signaling pathway in a dose-dependent manner to exert anticancer activity. In conclusion, our data suggest that 10b may be a new lead compound for further development of ROR1 inhibitors as anti-cancer agents.

Naringenin (1, Scheme 1) is a flavanone belonging to a part of a huge group of bioactive polyphenols. In order to selectively modify desired phenol/s, in this study, we developed some methods for selective protections of three hydroxy groups of 1. The 1st method is to silylate two hydroxy groups of 1 and then selectively de-protect the silylation product followed by site-selective acetylation, or site-selective silylation of 7-OH and then acetylation of 4’-OH. The 2nd synthetic method was started from triacetyloxylated naringenin (10), which was conducted in specific solvents to remove the distinctive acetyl protection by TFA, TsOH or imidazole. After protection of 4’,5-dihydroxynaringenin (12) by TBS at 7-OH to form 7-t-butyldimethylsilyloxy-4’,5-diacetyloxynaringenin (13), in the 3rd method, 4’-OAc or 5-OAc of 13 was selectively de-protected under acidic conditions to afford 4’-OH-5-OAc-7-OTBS naringenin (14) or 4’-OAc-5-OH-7-OTBS naringenin (6) as mixed protection derivatives. These methods have the advantages of mild reaction conditions, easily handled reagents and satisfactory yields.

Desmosine (1) and isodesmosine (2) are 1,3,4,5- and 1,2,3,5-tetrasubstituted pyridiniums and exist only in the extracellular matrix protein elastin as major crosslinking amino acids. They are formed by the condensation and cyclization of one lysine and three allysines, generated from lysine by lysyl oxidase. Since the discovery of desmosines in 1964, there have been no reports on their chemical synthesis for decades. The first total synthesis of 1 was reported in 2012 and since then, isodesmosine (2), desmopyridine (3), isodesmopyridine (4), neodesmosine (5), and merodesmosine (6) have been synthesized. Isotopically labeled desmosines have also been synthesized for the precise analysis of desmosines using isotope-dilution LC–MS/MS analysis. Synthesis of conjugates with desmosines and carrier proteins was achieved for antibody production. This review summarizes a series of desmosine syntheses based on cross-coupling reactions and Chichibabin pyridinium synthesis as synthesis methodologies. The obtained results would help in the development of novel diagnostic and therapeutic methodologies for elastin-degradation-related diseases.

Hexamethylphosphorous triamide (HMPT)-assisted and Fe2O3-nanoparticles (NPs) catalysed approaches towards the formation of C-N bond is described by the reaction between azoles and enone-compounds. The transformations were accomplished under mild conditions at temperatures 25 °C and 50 °C respectively. The efficacy and robustness of the reaction conditions can be envisioned by regioselective construction of N-heterocyclic scaffolds embedded with cycloalkyl residue. The established reaction conditions were found competent over a series of enones and azole derivatives to furnish the desired molecules in high yields ranging from 52-86% under P(III)-mediated conditions and 67-86% under the influences of Fe2O3-NPs as recyclable catalyst. It was observed that the catalyst can be recycled up to six times with good yields of the product.

(7S)-Macaureas A and B (1 and 2), two urea derivatives were isolated from the roots of Lepidium meyenii (Maca) collected from Qujing, Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic data, including 1D NMR, 2D NMR and HRESIMS techniques. The absolute configuration of (−)-1 was corrected as 7S by a concise three-step synthesis from commercially available Boc-L-proline. Macaureas A and B were tested for their cytotoxicities against five human cancer cell lines.

The chemistry of 3-(2-oxo-2H-chromen-3(6)(8)-yl)-1-aryl/heteroaryl-1H-pyrazole-4-carbaldehydes has gained increased interest in both synthetic organic and biological fields, since a large number of developments in the use of such compounds seem to be of considerable value. This review describes all the available synthetic methods for diverse 3-(2-oxo-2H-chromen-3(6)(8)-yl)-1-aryl/ heteroaryl-1H-pyrazole-4-carbaldehydes in the literature survey. It also summarizes thier chemical behaviors as building blocks towards a variety of chemical reagents to construct related compounds as well as their biological applications.