Chemistry - An Asian Journal最新文献

Dithiocarbamates (DTCs) are privileged scaffolds in medicinal chemistry, yet inaccessible via DNA-encoded libraries (DELs) due to a lack of robust on-DNA synthesis. We developed a general procedure for on-DNA DTC formation using a carbon disulfide (CS₂) bridging strategy. This method efficiently links diverse aliphatic secondary amines and alkyl halides under mild conditions with high conversions and excellent DNA compatibility. The utility of this method was demonstrated by constructing a prototype DEL, thereby bridging a critical gap in chemical space and facilitating the rapid discovery of DTC-based therapeutics.

The quantitative prediction of the π–π interaction energetics of the adsorption of polycyclic aromatic hydrocarbons (PAHs) on graphene remains a challenge, prompting the need for computationally efficient yet reliable methods. Herein, we investigated the intermolecular interactions of aromatic hydrocarbons, benzene, naphthalene, anthracene, pyrene, and coronene, with differently-sized nanographene models using the symmetry-adapted perturbation theory (SAPT) approach at the SAPT0 level. Convergence analysis of the total intermolecular interaction energies and the intervening components established circumcircumcoronene as the smallest nanographene model that can model the adsorption of the chosen aromatic hydrocarbons. The SAPT0 energies were then employed as the reference data for parametrizing an anisotropic analytic potential, namely the PAH anisotropic potential (PAHAP). The thus-parametrized PAHAP was subsequently employed to predict the most stable adsorption geometries of aromatic hydrocarbons over graphene. The estimated interaction energies and equilibrium distances differed significantly from those obtained using the original PAHAP parametrized against SAPT(DFT) interaction energies for small PAH dimers (J. Chem. Theory Comput., 2010, 6, 683–695). Nonetheless, single-point density functional theory electronic energy computation of both sets of PAHAP data yielded very similar energies, suggesting the competence of PAHAP parametrized against a comparatively low-demand computational approach like SAPT0 in modeling π–π interactions.

The ─N─N─ bond-containing alkyl hydrazine molecules are widespread in many natural products and biologically active drug molecules. In this context, a developed Ru-NHC complex 1, appended with Lewis acidic boron functionality in the secondary coordination sphere, was employed as an efficient catalyst for the selective deoxygenative hydrogenation of tertiary acylhydrazides to alkyl hydrazines using phenylsilane as a reductant under milder reaction conditions. Up to 92% of the selective tertiary alkyl hydrazine was achieved using a minimal silane concentration, without the formation of competitive N─N or C─N bond-cleaved products.

This work explores the synthesis of Cyclo[3]mer 1a obtained by the acid-catalyzed condensation reaction of 1,5-di(1H-pyrrol-2-yl)anthracene with pentafluorobenzaldehyde in the presence of trifluoroacetic acid. Because of the larger cavity size and multiple sites for coordination, cyclo[3]mer underwent smooth BF2 complexation which showed a triangle-like conformation based on the DFT optimization results. DFT analysis and solution state 1H NMR studies reveal the twisted C3 symmetric structure of the macrocycle 1a. Upon addition of enantiopure D and L mandelic acids, macrocycle 1a showed chiral response in CD spectra due to chirality induction.

Porphyrin-coumarin hybrid systems are an intriguing class of multifunctional hybrid molecules that combine the appealing photophysical properties of porphyrins with the biological significance of coumarins. This work introduces a new entry into this field, called porphyrin-azocoumarins 4–6. The porphyrins used in this study feature five-membered meso-tris(2-thienyl/2-furyl) substituents, in addition to meso-tris(4-tolyl) substituted porphyrins. This paper presents the synthesis, photophysical studies, and computational analysis of all the new hybrids reported. Furthermore, antimicrobial studies, in vitro cytotoxicity evaluations, and molecular docking analyses of these hybrids are reported. The hybrid 4 demonstrated excellent antibacterial activity and achieved the highest molecular docking scores in the series. All hybrids exhibited low in vitro cytotoxicity against NIH3T3 cell lines, suggesting their potential for further investigation as therapeutic agents.

The polarity changes of subcellular organelles have a profound influence on numerous pathological and biological processes, thus the accurate sensing of polarity changes in lysosomes, an important subcellular organelle, is essential for investigating the role and mechanisms of polarity in pathophysiological processes. Herein, we present ROMO, a rhodol-based fluorescent probe designed to target lysosomes by incorporating a morpholine moiety and featuring a tunable spirocyclic ring that opens and closes in response to polarity variations. ROMO maintains its nonfluorescent spirocyclic form in low-polarity environments, whereas it undergoes a progressive conversion into the red-emitting zwitterionic form as the polarity rises, showing a good linear correlation between fluorescence intensity and solvent polarity. Notably, ROMO was effectively applied to monitor lysosomal polarity in living cells, encompassing young and senescent cells from diverse cell lines. The research findings revealed that the lysosomal polarity in healthy cells was notably higher than that in cancer cells, and it gradually elevated with the progression of cellular senescence.

Autocatalysis refers to a synthetic transformation where products boost their own formation, while photochemistry enables innovative reaction pathways that can go beyond those by thermal activation. For the modern synthetic methodology development, the efficiency of autocatalysis and the versatility of photocatalysis have both played pivotal roles in this field and have recently merged into an emerging concept: photo-autocatalysis, which represents light-driven reactions featuring self-accelerated kinetics. From a mechanisticperspective, we systematically categorize these reactions based on the identity of key species responsible for photo-autocatalysis. These reactions can proceed with a single photo-autocatalyst that triggers photochemical transformation in an autocatalytic manner, or with a pair of photocatalyst and autocatalyst. For the former, it can be further categorized by whether the photo-autocatalyst is the product itself or an in situ generated complex, each offering distinct advantages. In this perspective, we present a classification framework and in-depth mechanistic discussion and offer insights into the design principles, key influencing factors, and future prospects of photo-autocatalysis, therefore contributing to the comprehension of this emerging topic.

Molecules containing a tertiary α-hydroxy carbonyl moiety are vital building blocks for synthesizing pharmaceuticals and natural products. In this study, we present an efficient rhodium(I)-catalyzed enantioselective allylation of α-ketoesters, providing a direct route to tertiary α-hydroxy esters. Operating at 5 °C, the method employs various α-ketoesters and allylBpin reagents to deliver the enantiomerically enriched tertiary homoallylic α-hydroxyesters bearing quaternary centers in high yields (up to 99%), excellent enantioselectivity (up to 98% ee), and diastereoselectivity (dr > 20:1). Demonstrating its synthetic utility, this protocol enables a five-step linear synthesis of lactone 13—a key precursor for anti-HIV and anticancer nucleoside analogues—from homoallylic alcohol 5af in a remarkable 85% overall yield.

Cancer remains a leading cause of death worldwide, reinforcing the need for new therapeutics. Natural products—particularly terpenoids—continue to yield potent anticancer agents and inspire novel biological targets. Within this space, sesterterpenoids (C25) form a smaller yet influential class whose intricate polycyclic architectures have hindered systematic SAR exploration. Advances in modern synthesis now enable efficient access to these molecules and their analogs, accelerating biological studies and design. This review article surveys representative total syntheses of polycyclic sesterterpenoids (≥3 rings), focusing on phorbaketals, ophiobolins, salmahyrtisol A, and scalaranes. Their reported bioactivities span from nano- to micromolar cytotoxicity against various cancer cell lines. Synthetic strategies toward phorbaketals feature gold-catalyzed spiroketalization and late-stage diversification. Ophiobolin routes assemble 5–8–5 frameworks using Nozaki–Hiyama–Kishi coupling, radical cascades, and atom-transfer/radical polyene cyclizations. A biomimetic synthesis of salmahyrtisol A leverages Friedel–Crafts construction of a pentacycle from sclareol-derived precursors. Scalarane syntheses employ reductive Heck cyclization, titanocene(III)-mediated polycyclizations, and intramolecular Diels–Alder reactions to forge dense stereochemical arrays and furan-annulated cores. Collectively, these advances deliver scalable access, clarify steric and conformational controls governing reactivity, and create opportunities for SAR-driven optimization of anticancer sesterterpenoids.