3,4-Fused pyrrolocoumarins, synthetically prepared or naturally occurring, possess interesting biological properties. In this review, the synthetic strategies for the synthesis of the title compounds are presented along with their biological activities. Two routes are followed for that synthesis. In one, the pyrrole ring is formed from coumarin derivatives, such as aminocoumarins or other coumarins. In the other approach, the pyranone moiety is built from an existing pyrrole derivative or through the simultaneous formation of coumarin and pyrrole frameworks. The above syntheses are achieved via 1,3-dipolar cycloaddition reactions, Michael reaction, aza-Claisen rearrangement reactions, multi-component reactions (MCR), as well as metal-catalyzed reactions. Pyrrolocoumarins present cytotoxic, antifungal, antibacterial, α-glucosidase inhibition, antioxidant, lipoxygenase (LOX) inhibition, and fluorescent activities, as well as benzodiazepine receptor ability.

The reaction mechanism of tthe formation of azomethine ylides from isatins and sarcosine is addressed in the literature in a general manner. This computational study aims to explore the mechanistic steps for this reaction in detail and to assess the reactivity of formed ylide in a 1,3-dipolar cycloaddition reaction with 7-oxabenzonorbornadiene. For this purpose, density functional theory (DFT) calculations at the M06-2X(SMD,EtOH)/6-31G(d,p) level were employed. The results indicate that CO2 elimination is the rate-determining step, the activation barrier for 1,3-dipolar cycloaddition is lower, and the formed ylide will readily react with dipolarophiles. The substitution of isatine with electron-withdrawal groups slightly decreases the activation barrier for ylide formation.

Cycloaddition reactions play a pivotal role in synthetic chemistry for the direct assembly of cyclic architectures. However, hurdles remain for extending the C4 synthon to construct diverse heterocycles via programmable [4+n]-cycloaddition. Here we report an atom-economic and modular intermolecular cycloaddition using furan-fused cyclobutanones (FCBs) as a versatile C4 synthon. In contrast to the well-documented cycloaddition of benzocyclobutenones, this is a complementary version using FCB as a C4 reagent. It involves a C-C bond activation and cycloaddition sequence, including a Rh-catalyzed enantioselective [4 + 2]-cycloaddition with imines and an Au-catalyzed diastereoselective [4 + 4]-cycloaddition with anthranils. The obtained furan-fused lactams, which are pivotal motifs that present in many natural products, bioactive molecules, and materials, are inaccessible or difficult to prepare by other methods. Preliminary antitumor activity study indicates that 6e and 6 f exhibit high anticancer potency against colon cancer cells (HCT-116, IC50 = 0.50 ± 0.05 μM) and esophageal squamous cell carcinoma cells (KYSE-520, IC50 =  0.89 ± 0.13 μM), respectively.

1,2,4-Triazoles are privileged scaffolds for many pharmaceuticals, and methods for structurally diverse compound libraries are of current interest. Here we report an efficient coupling of α-diazoacetates with amino acid-derived alkyl N-hydroxy phthalimide esters, under metal-free conditions involving 1,8-diazabicyclo(5.4.0)undec-7-ene as the base, with which highly functionalized 1,2,4-triazoles can be obtained in excellent yields with remarkable functional group tolerance. Preliminary studies revealed that 1,2,4-triazole 3a exhibits potent inhibition of tyrosinase activities in melanoma B16F10 cell lines, demonstrating promising skin-whitening properties.

Lipidomics by high-resolution mass spectrometry (HRMS) has become a prominent tool in clinical chemistry due to the proven connections between lipid dysregulation and the insurgence of pathologies. However, it is difficult to achieve structural characterization beyond the fatty acid level by HRMS, especially when it comes to the regiochemistry of carbon-carbon double bonds, which play a major role in determining the properties of cell membranes. Several approaches have been proposed for elucidating the regiochemistry of double bonds, such as derivatization before MS analysis by photochemical reactions, which have shown great potential for their versatility but have the unavoidable drawback of splitting the MS signal. Among other possible approaches for derivatizing electron-rich double bonds, the emerging inverse-electron-demand Diels-Alder (IEDDA) reaction with tetrazines stands out for its unmatchable kinetics and has found several applications in basic biology and protein imaging. In this study, a catalyst-free click IEDDA reaction was employed for the first time to pinpoint carbon-carbon double bonds in free and conjugated fatty acids. Fatty acid and glycerophospholipid regioisomers were analyzed alone and in combination, demonstrating that the IEDDA reaction had click character and allowed the obtention of diagnostic product ions following MS/MS fragmentation as well as the possibility of performing relative quantitation of lipid regioisomers. The IEDDA protocol was later employed in an untargeted lipidomics study on plasma samples of patients suffering from prostate cancer and benign prostatic conditions, confirming the applicability of the proposed reaction to complex matrices of clinical interest.

Click chemistry is widely used for the efficient synthesis of 1,4-disubstituted-1,2,3-triazole, a well-known scaffold with widespread biological activity in the pharmaceutical sciences. In recent years, this magic ring has attracted the attention of scientists for its potential in designing and synthesizing new antifungal agents. Despite scientific and medical advances, fungal infections still account for more than 1.5 million deaths globally per year, especially in people with compromised immune function. This increasing trend is definitely related to a raise in the incidence of fungal infections and prevalence of antifungal drug resistance. In this condition, an urgent need for new alternative antifungals is undeniable. By focusing on the main aspects of reaction conditions in click chemistry, this review was conducted to classify antifungal 1,4-disubstituted-1,2,3-triazole hybrids based on their chemical structures and introduce the most effective triazole antifungal derivatives. It was notable that in all reactions studied, Cu(I) catalysts generated in situ by the reduction in Cu(II) salts or used copper(I) salts directly, as well as mixed solvents of t-BuOH/H2O and DMF/H2O had most application in the synthesis of triazole ring. The most effective antifungal activity was also observed in fluconazole analogs containing 1,2,3-triazole moiety and benzo-fused five/six-membered heterocyclic conjugates with a 1,2,3-triazole ring, even with better activity than fluconazole. The findings of structure-activity relationship and molecular docking of antifungal derivatives synthesized with copper-catalyzed azide-alkyne cycloaddition (CuAAC) could offer medicinal chemistry scientists valuable data on designing and synthesizing novel triazole antifungals with more potent biological activities in their future research.

Nucleic acids play a pivotal role in the diagnosis of diseases. However, rapid, cost-efficient, and ultrasensitive identification of nucleic acid targets still represents a significant challenge. Herein, we describe an enzyme-free DNA amplification method capable of achieving accurate and ultrasensitive nucleic acid detection via DNA-templated click ligation chain reaction (DT-CLCR) catalyzed by a heterogeneous nanocatalyst made of Cu2O (hnCu2O). This hnCu2O-DT-CLCR method is built on two cross-amplifying hnCu2O-catalyzed DNA-templated azide-alkyne cycloaddition-driven DNA ligation reactions that boast a fast reaction rate and a high DNA ligation yield in minutes, enabling rapid exponential amplification of specific DNA targets. This newly developed hnCu2O-DT-CLCR-enabled DNA amplification strategy is further integrated with two signal reporting mechanisms to achieve low-cost and easy-to-use biosensors: an electrochemical sensor through the conjugation of a methylene blue redox reporter to a DNA probe used in hnCu2O-DT-CLCR and a colorimetric sensor through the incorporation of the split-to-intact G-quadruplex DNAzyme encoded into hnCu2O-DT-CLCR. Both sensors are able to achieve specific detection of the intended DNA target with a limit of detection at aM ranges, even when challenged in complex biological matrices. The combined hnCu2O-DT-CLCR and sensing strategies offer attractive universal platforms for enzyme-free and yet efficient detection of specific nucleic acid targets.

The cycloaddition of CO2 to epoxides to afford versatile and useful cyclic carbonate compounds is a highly investigated method for the nonreductive upcycling of CO2. One of the main focuses of the current research in this area is the discovery of readily available, sustainable, and inexpensive catalysts, and of catalytic methodologies that allow their seamless solvent-free recycling. Water, often regarded as an undesirable pollutant in the cycloaddition process, is progressively emerging as a helpful reaction component. On the one hand, it serves as an inexpensive hydrogen bond donor (HBD) to enhance the performance of ionic compounds; on the other hand, aqueous media allow the development of diverse catalytic protocols that can boost catalytic performance or ease the recycling of molecular catalysts. An overview of the advances in the use of aqueous and biphasic aqueous systems for the cycloaddition of CO2 to epoxides is provided in this work along with recommendations for possible future developments.

Tung oil is commonly utilized for coating protection in wooden products, often attracting attention for its appearance, antimicrobial capabilities, and insect-resistant coatings. However, its poor mechanical properties and poor weather resistance stem from excessive self-crosslinking of surplus conjugated double bonds and molecular chains, resulting in poor film wrinkling. Therefore, this study introduces natural rubber via the Diels-Alder reaction to consume the residual double bonds in tung oil, resulting in tung oil/natural rubber composite coatings (NRTO) with excellent mechanical properties and weather resistance. The results indicate that NRTO exhibits excellent mechanical properties, including high elongation (32 %) and strong adhesion (4.55 MPa). Furthermore, NRTO demonstrates outstanding acid resistance and UV aging resistance. Given its many benefits, NRTO film emerges as a promising candidate for substantially protecting wood surfaces in demanding environments.

The deep-sea fungus Phomopsis lithocarpus FS508 produces tenellone-macrolide conjugated hetero-dimer lithocarpins A-G with anti-tumor activities. The deficiency of new intermolecular Diels-Alder (DA) enzymes hindered the development of new bioactive hetero-dimers. A novel single-function intermolecular DA enzyme, g7882, was initially discovered in this study. The deletion of g7882 led to the disappearance of lithocarpin A and an increase in precursor level . the overexpression of g7882 significantly improved lithocarpin A yield. The in vitro function of g7882DA was also confirmed by biochemical reaction using tenellone B as a substrate. Additionally, the knockout of KS modules of PKS in cluster 41 and cluster 81 (lit cluster) eliminated the production of lithocarpins, which firstly explains the biosynthetic process of hetero-dimer lithocarpins mediated by DA enzyme in FS508. Furthermore, the removal of a novel acetyltransferase GPAT in cluster 41 and the oxidoreductase, prenyltransferase in cluster81 resulted in the reduction of lithocarpin A in P. lithocarpus. The overexpression of gpat in P. lithocarpus FS508 improved the yield of lithocarpin A significantly and produced a new tenellone derivative lithocarol G. This study offers a new DA enzyme tool for the biosynthesis of novel hetero-dimer and biochemical clues for the biosynthetic logic elucidation of lithocarpins.