Organic & Biomolecular Chemistry最新文献

In this study, we introduce an electrocatalytic reaction for hydrogenating alkynes to Z-alkenes, which demonstrates exceptional efficiency with high chemo- and stereoselectivity. Control experiments reveal that hydrogen primarily originates from the solvent, supporting a mechanism where palladium catalyzes continuous hydrogen adsorption and transfer under cathodic conditions. The synthetic value of the Z-alkene products, the mild, green nature of the method, and successful gram-scale experiments underscore the potential of this approach for practical and industrial applications, offering a more sustainable and scalable alternative to traditional catalytic processes for selective alkene synthesis.

Herein, we present the first synthesis of hybrid molecules combining the pharmacophores of two natural compounds, schweinfurthin E (SW-E) and the glycosidic moiety of OSW-1. These hybrids were designed leveraging the complementary binding of SW-E and OSW-1 to their biological target. The synthetic process highlights, in particular, one-pot functionalization and glycosylation of an L-arabinose unit using a D-xyloside donor and a CuAAC click reaction involving a polyfunctionalized prenylated stilbene derived from SW-E. The cytotoxicity of the four SW-E and OSW1 hybrids is also reported, two of them being much more cytotoxic than SW-E on a glioblastoma cancer cell line. Finally, a molecular modeling study is conducted to rationalize the biological results obtained.

Dynamic covalent macrocycles offer the advantage of tunable ring-opening/ring-closure and structural transformation, but their control with precision remains a daunting task due to the labile nature of reversible bonds. Herein we demonstrate the precise formation/scission of covalent macrocycles with varied sizes by contrasting the reactivity, stability, and degradability of light-active and light-inactive dynamic covalent bonds. The incorporation of photoswitchable and non-photoresponsive aldehyde sites into one single dialdehyde component afforded the creation of [1 + 1] type macrocycles with primary diamines of suitable lengths. The manipulation of light and acid/base stimuli allowed on-demand breaking/remaking of macrocycles, achieving the interconversion between macrocyclic and linear skeletons. Moreover, a combination of the dialdehyde, primary diamines, and secondary diamines enabled the construction of hetero-type [2 + 1 + 1'] macrocycles via enhanced discrimination and hierarchical assembly. Light-induced kinetic locking/unlocking of dynamic bonds further afforded macrocycle-to-macrocycle conversion when needed. Through leveraging controllable covalent connection/disconnection, switchable formation/disintegration of mechanically interlocked catenanes was further accomplished. The results described showcase the potential of photoinduced dynamic covalent chemistry for preparing complex architectures and should set the stage for molecular recognition, dynamic assemblies, synthetic motors, and responsive materials.

Photosensitizers (PSs) with robust pH stability and the ability to generate both type I and type II reactive oxygen species (ROS) have gained significant attention due to their versatility in various applications. In this study, we employed an electron donor-acceptor engineering strategy to design and synthesize a fluoran-triphenylamine photosensitizer (Fl-TPA), using an ester-protected ring-opened fluoran cation as the electron acceptor and triphenylamine (TPA) as the electron donor. Compared to fluoran with a spirolactone structure, Fl-TPA exhibits a significant redshift in absorption, with good light capture capabilities in the 300-600 nm range. In comparison with the reference compound Fl-H, which lacks the TPA group, Fl-TPA shows a substantial decrease in fluorescence intensity. Transient fluorescence measurements reveal biexponential decay characteristics for both compounds. Specifically, Fl-TPA shows τ₁ = 0.21 ns (41%) and τ₂ = 2.92 ns (59%), while Fl-H shows τ₁ = 0.14 ns (93%) and τ₂ = 2.23 ns (7%). The longer-lived component in Fl-TPA is more pronounced, suggesting the presence of additional non-radiative decay pathways, as further supported by the steady-state fluorescence analysis. Additionally, Fl-TPA exhibits a significant Stokes shift in solvents of varying polarity. Time-dependent density functional theory (TD-DFT) calculations reveal that the introduction of the strong electron-donating TPA group reduces the ΔE_S-T of Fl-TPA to 1.25 eV, which is significantly lower than that of Fl-H (1.46 eV), facilitating intersystem crossing (ISC). Thus, in the ROS generation experiment, it can be observed that Fl-H produces almost no ROS. In contrast, Fl-TPA not only exhibits high type I ROS generation capability, but also demonstrates excellent type II and total ROS generation capabilities, with performance far superior to the clinically approved near-infrared PS, indocyanine green (ICG). Moreover, Fl-TPA exhibits excellent pH stability compared to the non-esterified fluoran. The results of this study present a new photosensitizer with strong ROS generation capability and good stability across a wide pH range, providing a theoretical foundation for the design of PSs.

2-Hydroxy-1,4-naphthoquinone, widely recognized as lawsone, is a natural dye obtained from the henna plant (Lawsonia inermis), known for its biological activity and diverse applications in biochemistry and analytical chemistry. As a versatile precursor, it plays a crucial role in synthesizing a wide range of structurally diverse and bioactive molecular scaffolds. This review highlights recent progress in the development of lawsone derivatives, emphasizing their extensive biological activities, such as anticancer, antimicrobial, antioxidant, antimalarial, and metabolic enzyme-targeting activities, as well as their structure-activity relationships. Remarkably, this is the first detailed exploration covering both the biological activities and chemical synthesis of significant lawsone derivatives from 2016 to the present.

We present a concise asymmetric synthesis of (-)-Bao Gong Teng A, a 2-hydroxylated tropane alkaloid with hypotensive and miotic activities isolated from the Chinese herb Erycibe obtusifolia Benth. Using an Evans chiral auxiliary, we achieve a regio- and stereoselective 1,3-dipolar cycloaddition between p-chlorobenzyl pyridinium salt and (R)-3-acryloyl-4-phenyloxazolidin-2-one, efficiently generating the tropane skeleton on a decagram scale. This methodology provides a rapid and practical synthesis of optically active (-)-Bao Gong Teng A for further biological studies.

A new cleavable azo linker was synthesized and reacted with 5-iodo-2'-deoxyuridine, followed by triphosphorylation, and finally labeled with Cy3 to give the desired product dUTP-azo linker-Cy3 as a potential reversible terminator for DNA sequencing. The synthesized 3'-OH-unblocked nucleotide triphosphate can be faithfully incorporated into the DNA strands as catalyzed by DNA polymerase (Bst 3.0) with 100% yield. Meanwhile, further incorporation is terminated temporarily by the overall steric hindrance of the nucleotide triphosphate, ensuring that only one molecule can be incorporated into the DNA strand within one sequencing cycle even for a template containing multiple identical bases in a row. The next incorporation can proceed smoothly upon complete removal of the labeled dye with only aniline left on the elongated DNA strand. The synthesized nucleotide triphosphate is the first reversible terminator that can be considered crucial for DNA sequening. These preliminary evaluations indicate that the synthesized nucleotide triphosphate holds substantial potential value in DNA sequencing.

In this study, we evaluate the performance of the DP4+ and MM-DP4+ methods on molecules featuring small heterocyclic rings. A dataset of 71 molecules containing three- and four-membered heterocycles, known for their stereochemical assignment challenges, was analyzed. We compared molecular geometries optimized at different computational levels, including MMFF and B3LYP/6-31G*, to assess deviations in key geometric parameters relative to the heterocycle structures. Furthermore, the geometric properties of these molecules were investigated using various force fields to evaluate their differences. Our aim was to assess the reliability of B3LYP/6-31G* in comparison with more accurate methods and to elucidate how different force fields influence in geometric precision.

In this study, we present the first catalytic methodology for synthesizing N-methyl secondary amides via dehydrative condensation of hydroxycarboxylic acids with readily available and safe aqueous methylamine, employing diboronic acid anhydride (DBAA) as the catalyst. DBAA catalysis can also be applied to direct amidations using aqueous ethylamine or aqueous dimethylamine. Moreover, we demonstrate the applicability of this catalytic system for the concise synthesis of eight biologically active compounds containing β-amino alcohol motifs, including halostachine, synephrine, longimammine, phenylephrine, metanephrine, normacromerine, etilefrine, and macromerine.

The abnormal size and number of lipid droplets (LDs) are closely associated with a variety of diseases, including metabolic syndrome related diseases, liver disease and tumors. Therefore, it is particularly important to develop a fluorescent probe that can monitor the abnormal state of LDs. In this study, we designed and synthesized four compounds (namely TCO1, TCO2, TCN1 and TCN2) using coumarin derivatives as the fundamental building blocks. Notably, the fluorescence spectra of compounds TCO1 and TCO2 revealed distinct AIE properties in systems with different ratios of ethanol/water. Furthermore, cell imaging study of compound TCO1 exhibited negligible background fluorescence, indicating its efficacy as a washing-free fluorescent probe targeting LDs within cells. Moreover, cell imaging results for compound TCO1 showed substantial overlap with those obtained from LD commercial dye, thereby confirming its capability to specifically target LDs. Additionally, compound TCO1 was able to monitor changes in both size and quantity of LDs induced by oleic acid stimulation, as well as to discriminate between normal organs and tumours. Based on these properties, compound TCO1 developed in this study provides an effective method for detecting LD abnormalities, a novel technique for visualizing tumor sites in vitro, and also provides new insights for the detection of other related diseases.