Beilstein Journal of Organic Chemistry最新文献

Integrating molecular photoswitches into rotaxanes offers unique opportunities for precise control over their structural, dynamic, and functional properties. By harnessing light as a non-invasive stimulus with high spatial and temporal resolution, these photoswitches allow for the modulation of the rotaxanes' intra- and intermolecular interactions, optoelectronic properties, and shuttling dynamics. In this review, we discuss key examples of photoswitchable rotaxanes, organized according to the position of the photoswitch, either embedded in the axle or incorporated into the macrocycle. We examine the major classes of photoswitches used, including their switching mechanisms and the resulting influence on rotaxane operation. Due to their architectural versatility and precise light control, photoswitchable rotaxanes hold promise for a broad range of applications, including light-responsive molecular machines, smart materials, and biofunctional systems. However, emerging applications increasingly require rethinking and developing new structural designs that incorporate more efficient and advanced photoswitches to fully realize their potential.

In recent years, the Norrish-Yang cyclization and related photoredox reactions of dicarbonyls have been extensively utilized in natural product synthesis. This review summarizes the latest advancements in these reactions for constructing terpenoids, alkaloids, and antibiotics. Through Norrish-Yang cyclization, dicarbonyls (e.g., 1,2-diketones and α-keto amides) can efficiently construct sterically hindered ring structures, which can further undergo ring-opening or rearrangement reaction to assemble complex molecular frameworks. Additionally, quinone photoredox reactions involving single-electron transfer (SET) processes provide novel strategies for the stereoselective synthesis of useful structures such as spiroketals. This review, drawing on examples from recently reported natural product syntheses, elaborates on reaction mechanisms, factors governing regioselectivity and stereoselectivity, and the impact of substrate structures on reaction pathways. These reactions not only serve as robust tools for the streamlined synthesis of natural products but also establish a solid foundation for subsequent pharmaceutical investigations.

In this review, we summarize and compare four total syntheses of complanadine A, a complex and pseudo-dimeric lycopodium alkaloid with promising neurotrophic activity and potential for pain management. These four total syntheses are from the groups of Siegel, Sarpong, Tsukano, and Dai. Each of the four total syntheses contains innovative strategies and creative tactics, reflecting how emerging synthetic capabilities and concepts can positively impact natural product total synthesis.

Contamination of water bodies by micropollutants including industrial dyes is a worldwide health and environmental concern. We report the design, synthesis, and characterization of a series of methylene-bridged glycoluril dimers G2W1-G2W4 that are insoluble in water and that differ in the nature of their aromatic sidewalls (G2W4: benzene, G2W3: naphthalene, G2W1 and G2W2: triphenylene). We tested G2W1-G2W4 along with comparator H2 as solid-state sequestrants for a panel of five dyes (methylene blue, methylene violet, acridine orange, rhodamine 6G, and methyl violet 6B). We find that catechol-walled H2 (OH substituents) is a superior sequestrant compared to G2W1-G2W4 (OMe substituents). X-ray crystal structures for G2W1 and G2W3 suggest that the OMe groups fill their own cavity and thereby decrease their abilities as sequestrants. H2 achieved a removal efficiency of 94% for methylene blue whereas G2W1 demonstrated a 64% removal efficiency for methylene violet; both sequestration processes were largely complete within 10 minutes.

Halogenated butyrolactones are found in a variety of bioactive materials and used for the construction of nucleoside analogues. Short procedures for their synthesis have been developed starting with levoglucosenone, which can be obtained in a single step from the pyrolysis of acid-treated cellulose. The processes use inexpensive reagents for the stereoselective C3 functionalization of the bicyclic ring system, with a subsequent Baeyer-Villiger oxidation affording the fluorinated, chlorinated, and brominated dideoxyribonolactones.

This perspective is focused on enantioselective free radical reactions. It describes several important catalytic asymmetric strategies applied to enantioselective radical reactions, including chiral Lewis acid catalysis, organocatalysis, photoredox catalysis, chiral transition-metal catalysis and photoenzymatic catalysis. The application of electrochemistry to asymmetric radical transformations is also discussed.

This review presents a paradigm-shifting "pathway economy" strategy for 1,n-enyne cyclization, enabling divergent construction of complex molecular architectures from a single substrate class. Through mechanistic-guided modulation of catalysts, solvents, ligands, and angle strain, this approach achieves unprecedented reaction pathway control while demonstrating superior temporal and step efficiency compared to conventional methods. The work establishes a sustainable framework for rapid molecular diversification, offering transformative potential for green chemistry and pharmaceutical applications. By unifying mechanistic insights with practical synthetic design, this review provides valuable guidance for future innovations in precision organic synthesis.

The cdc2-like kinases (CLKs), are a family of kinases that attracted recently the interest of scientists due to their significant biological roles, in particular in the regulation of the mRNA splicing process. Among the four isoforms of CLKs, CLK3 is the one for which the biological roles are less understood, in part because no selective inhibitor of this challenging kinase has been found to date. Based on structural analysis of the CLKs we have identified the lysine 241, present only in CLK3, as an attractive residue to design inhibitors with increased affinity towards this kinase as compared to the three other isoforms CLK1, CLK2, and CLK4. Based on this observation, we have been able to transform a molecule (DB18) previously established with a very low activity on CLK3 into a derivative VS-77 which has now a significant affinity toward CLK3 (IC₅₀ = 0.3 μM). Thus, VS-77 appears as a new pan-inhibitor of the CLK family.

A terminal 3-methylpent-4-en-2-ol (MPO) moiety is a common structural feature in various polyketide natural products. Stereochemical assignments of this moiety have mainly relied on computational analyses of NMR, ECD, and specific rotation data. However, none of these approaches can be applied to all compounds. In this study, we developed a method to determine the absolute configuration of the terminal MPO moiety with high accuracy and sensitivity by a combination of chemical degradation, chemical synthesis, and chiral LC-MS analysis. The applicability of this method was demonstrated through the stereochemical assignment of (+)-capsulactone (1).

Azobenzenes are photoresponsive compounds widely used in molecular switches, light-controlled materials, and sensors, but despite extensive studies on symmetric derivatives, efficient methods for synthesizing non-symmetric analogues remain scarce due to regioselectivity issues, multistep procedures, and limited applicability to tetra-ortho-substituted structures. Herein, we describe a direct, one-pot Pd-catalyzed dehydrogenative C-N coupling between aryl bromides and arylhydrazines to access non-symmetric azobenzenes. The use of bulky phosphine ligands and sterically tuned substrates promotes selective N-arylation at the terminal nitrogen. The protocol tolerates a wide range of functional groups and enables the synthesis of well-decorated azobenzenes, including tetra-ortho-substituted derivatives. Notably, the reaction proceeds under an O₂ atmosphere and in the presence of water, highlighting its robustness.