Long-term exposure to ultraviolet (UV) radiation can cause sunburn, skin aging, and skin cancers. Conventional sunscreens typically combine organic UV filters and inorganic particles for photoprotection, yet concerns remain regarding skin penetration, systemic effects, and reactive oxygen species generation. Inspired by natural photoprotective mechanisms in plants, we develop a series of all-small-molecule sunscreen hydrogels based on natural polyphenols through a facile one-pot assembly process. The resulting hydrogels exhibit efficient UV shielding with high sun protection factors, strong bioadhesion, antioxidant and antibacterial activities, high visible-light transmittance, and low skin penetration tendency. The hydrogels also demonstrate good environmental stability and effective photoprotection in both mice and Bama miniature pigs. This work highlights the potential of bioinspired all-small-molecule assemblies for efficient and safe photoprotection.

The stereoselective construction of fluorinated architectures is of great importance in medicinal chemistry, as fluorination can profoundly improve the pharmacokinetic profiles of bioactive molecules. Nonetheless, the enantioselective synthesis of fluorine-containing natural product derivatives continues to pose a significant challenge. In this work, we describe a highly exo- and enantioselective Diels-Alder reaction enabled by a novel diboronate complex generated from bispyrrolidine diboronate (BPDB) in combination with Lewis and Brønsted acids. This strategy provides efficient access to structurally diverse fluorinated abietane diterpenes with high stereocontrol.

The highly congested fused tetracyclic core of cipadonoid A and harpertrioate A has been constructed using visible-light photoredox-catalyzed intramolecular Giese-type radical cyclization as a key step. The developed chemistry paves the way for the total synthesis of this family of biologically important natural products.

From both structural and functional perspectives, the large family of α-methylene-γ-lactone-type cembranolides represents a remarkable class of natural products. As potent lead compounds for anti-inflammatory, antiviral, and antifibrotic applications, their therapeutic potential continues to attract extensive investigation. Nevertheless, synthetic routes to such cembranolides remain scarce. Herein, we report a distinctive skeletal integration strategy to access this class of complex diterpenes from the naturally abundant precursor (+)-costunolide. This approach leverages a highly regioselective ring-opening metathesis (ROM), an enantioselective Rh-catalyzed asymmetric allylic substitution, and a tandem ring-opening metathesis/ring-closing metathesis (ROM/RCM) reaction. Notably, the strategy enables a concise 5-step semisynthesis of the flagship cembranolide, ovatodiolide, for the first time. This modular route offers a general means to access ovatodiolide-type cembranolides, thereby facilitating structure-activity relationship studies within this biologically significant family.

Selective methylation of aromatics using CO2/H-2 presents a promising avenue for producing high-value-added chemicals with high selectivity. Herein, we introduced atomically dispersed Pd species into ZnZrOx solid solution and combined with HZSM-5 to create a bifunctional catalyst, applying to selectively synthesize para-xylene through toluene methylation using CO2/H-2 at low pressure. Remarkably, 0.1 wt% Pd in PdZnZrOx-HZSM-5 afforded the selectivity of xylene in CO-free products and para-xylene in xylene to 90.0% and 85.6% at 0.5 MPa, respectively. Spectroscopic characterizations revealed that atomically dispersed Pd species enhance the dissociation of adsorbed hydrogen and facilitate the creation of oxygen vacancies, benefiting the CO2 hydrogenation to CHxO intermediates. Density functional theory calculations suggested that Pd-doped ZnZrOx reduces the energy barrier for hydrogenating H2COOH* to H2CO*, aiding to form CH3O* intermediate for toluene methylation. This work provides insights into the design of catalysts for the selective methylation of aromatics using CO2/H-2 at low pressure.

A rhodium(III)-catalyzed dual-ring formation via cascade C-H activation/[4 + 2] annulation of 3,5-diaryoxadiazoles with alkynes was developed. This strategy has been demonstrated with a variety of 3,5-diaryloxadiazoles and alkynes, and it has been successfully scaled up to gram-scale synthesis, highlighting its potential significance in the direct construction of C-N atropisomers. Furthermore, the cleavage of the N-O bond is essential for the formation of the bicyclic structure in the absence of an external oxidant. Mechanistic studies revealed that cleavage of the C-H bond at the 3-phenyl group of oxadiazole was likely a rate-determining step in this reaction.

This study presents a streamlined stereoselective synthesis strategy for constructing the highly congested cage-like tetracyclic core of cipadonoid A, employing visible-light photoredox catalysis to enable intramolecular Giese-type radical cyclization as a key step. Density Functional Theory (DFT) analysis revealed that the selective formation of the cis-fused AB bicyclic framework is controlled by intramolecular hydrogen bonding-mediated conformational stabilization. Notably, the synthesized B,D-seco-limonoid scaffold exhibited lysosomal biogenesis enhancing activity on par with its natural counterpart, with comparative bioassays demonstrating equivalent efficacy between the synthetic derivative and native cipadonoid A (1) in promoting lysosomal biogenesis.

The asymmetric total synthesis of janthinoid A has been accomplished for the first time in 14 steps without using a protecting group. The trans-decalin subunit and the rigid oxabicyclo[3.2.1]octane motif were constructed via an epoxide-initiated cationic π-cyclization reaction and a Fe(ClO4)3-mediated oxidative cascade cyclization reaction, respectively.

Regio- and stereoselective photoredox-catalyzed cyclizations of alkene-substituted β-ketoesters have been accomplished for the synthesis of polyfunctionalized cyclopentanones. This was achieved using 2,3,5,6-tetrakis(carbazol-9-yl)-1,4-dicyanobenzene (4CzTPN) and 2,4,6-triisopropyl-thiophenol as cocatalysts under illumination of a blue-light-emitting-diode at ambient temperature. The developed chemistry was successfully applied in the enantioselective total synthesis of the tricyclic prostaglandin D2 metabolite (tricyclic-PGDM) methyl ester, which was completed in 9 steps with an overall yield of 7%.

Natural products with topologically complex architectures are important sources in drug discovery. The pursuit of conciseness and efficiency in the total synthesis of natural products promotes continuous innovation and the development of new reactions and strategies. In this work, a PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction of N-substituted cyclobutenone provided a facile approach to the direct construction of the ABCE tetracyclic framework of Aspidosperma alkaloids. DFT calculations showed that the rate-determining step of the key PET reaction involved C19–C12 bond formation and C19–C3 bond cleavage. Investigation of the bond length changes along the IRC path, spin density, and NBO analysis indicated that this process is neither strictly concerted nor stepwise, but falls in between, and involves a formal 1,3-C shift.

Developing versatile and reliable memristive devices is crucial for advancing future memory and computing architectures. The years of intensive research have still not reached and demonstrated their full horizon of capabilities, and new concepts are essential for successfully using the complete spectra of memristive functionalities for industrial applications. Here, we introduce two-terminal ohmic memristor, characterized by a different type of switching defined as filament conductivity change mechanism (FCM). The operation is based entirely on localized electrochemical redox reactions, resulting in essential advantages such as ultra-stable binary and analog switching, broad voltage stability window, high temperature stability, high switching ratio and good endurance. The multifunctional properties enabled by the FCM can be effectively used to overcome the catastrophic forgetting problem in conventional deep neural networks. Our findings represent an important milestone in resistive switching fundamentals and provide an effective approach for designing memristive system, expanding the horizon of functionalities and neuroscience applications.

Two conformers of a dipyrrolylbenzothiadiazole (DP-BTD) embedded decaphyrin(1.1.1.0.0.1.1.1.0.0) have been synthesized and separated, exhibiting crescent-shaped and figure-eight conformations, respectively. Incorporation of the hydrogen bonding-reinforced pseudorigid and electron-withdrawing DP-BTD segments not only stabilizes the distinct conformations, but also extends the absorption to ca. 1600 nm due to the good conjugation and ICT effect. Although both conformers are stable at room temperature, reversible interconversion occurs between them upon heating or disrupting intramolecular hydrogen bonds by protonation.

A photoredox-based oxidative heterocoupling of enolsilanes to the corresponding 1,4- and 1,6-dicarbonyl compounds was developed by using Mes-Acr(+)BF(4)(-) as the photocatalyst, and oxygen was used as the oxidant. This newly developed chemistry adheres to the principles of atom economy, step economy, and redox economy, making it a concise and efficient method.

A highly effective and enantioselective vinylogous Mannich reaction between benzothiazolimines and γ-butenolides catalyzed by a quinine based squaramide has been disclosed. A series of chiral benzothiazole amines containing a γ,γ-disubstituted butanolide scaffold bearing an adjacent chiral stereocenter have been successfully obtained in good to excellent yields (up to 91%) with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (>20 : 1 dr) with broad substrate generality under mild conditions. The new scaffold integrated with both chiral benzothiazolimine and γ-butenolide moieties may provide a possibility for the development of new pharmaceutical entities.

The Diels-Alder reaction stands as one of the most pivotal transformations in organic chemistry. Its efficiency, marked by the formation of two carbon-carbon bonds and up to four new stereocenters in a single step, underscores its versatility and indispensability in synthesizing natural products and pharmaceuticals. The most significant stereoselectivity feature is the "endo rule". While this rule underpins the predictability of the stereochemical outcomes, it also underscores the challenges in achieving the opposite diastereoselectivity, making the exo-Diels-Alder reactions often considered outliers. This review delves into recent examples of exo-Diels-Alder reactions, shedding light on the factors inverting the intrinsic tendency. We explore the roles of steric, electrostatic, and orbital interactions, as well as thermodynamic equilibriums in influencing exo/endo selectivity. Furthermore, we illustrate strategies to manipulate these factors, employing approaches such as bulky substituents, s-cis conformations, transient structural constraints, and innovative control physics. Through these analyses, our aim is to provide a comprehensive understanding of how to predict and design exo-Diels-Alder reactions, paving the way for new diastereoselective catalyst systems and expanding the chemical scope of Diels-Alder reactions.

The total syntheses of penicibilaenes A and B are described. The key step is the tBuOK/DMSO-mediated tandem 5-exo-dig Conia-ene type reaction and 6-exo-dig Conia-ene type reaction to install the tricyclic [6.3.1.01,5] dodecane core of penicibilaenes from dibutynyl cyclohexanone in a single step, together with a sequence of copper-mediated conjugate addition and Crabtree's hydrogenation to forge the stereogenic centers at C5 and C2, respectively.

A novel strategy for the synthesis of Aspidosperma alkaloids has been achieved via a photoredox-initiated [2+2]/retro-Mannich reaction of tryptamine-substituted enaminones as a key step. The developed chemistry has been applied to the construction of the core tetracycle of Aspidosperma alkaloids (±)-aspidospermidine and (±)-limaspermidine.

The Norrish-Yang reaction, as a typical example, demonstrates the inherent ability of photochemical reaction to facilitate formation of sterically congested C-C bonds, efficiently crafting intricate ring structure in complex organic molecules. Herein we report for the first time a unified synthesis using quinone-based acid-promoted Norrish-Yang photocyclization for the stereoselective construction of multiple avarane-type meroterpenoid natural products.

An I-2-promoted C-H arylselenylation of pyrrolo[1,2-a]quinoxalines with diaryl diselenides is developed, providing an efficient route to a series of 1 (or 3)-arylselenylated and/or 1,3-diaryl diselenylated pyrrolo[1,2-a]quinoxalines. The methodology is characterised by a wide range of substrates, good functional group tolerance and gram-level synthesis. Further transformations of the products to form structurally diverse pyrrolo[1,2-a]quinoxalines were successfully achieved. Similarly, I-2-promoted C-H sulfenylation of pyrrolo[1,2-a]quinoxaline with 1,2-diphenyldisulfane were investigated. We believe that these novel pyrrolo[1,2-a]quinoxaline compounds will have promising applications in pharmaceutical synthesis.

A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.