Organic & Biomolecular Chemistry最新文献

Over the past five years, maleimide scaffolds have gained considerable attention in organic synthesis for their role in forming cyclized molecules through annulation and C-H activation. As versatile and reactive coupling agents, maleimides have enabled the efficient synthesis of various cyclized products, including annulation, benzannulation, cycloaddition, and spirocyclization, with applications in medicinal chemistry, drug discovery, and materials science. Despite the extensive study of maleimide chemistry, certain reactions-such as cycloaddition-based annulation, photoannulation, and electrochemical transformations-remain underexplored despite their promising potential in the pharmaceutical and chemical industries. Recent advancements, such as photocatalysis and electrochemical methods, have expanded the utility of maleimides, providing more sustainable and selective approaches for synthesizing complex molecules. This review compiles research published between 2019 and 2024, highlighting the substrate scope, reaction diversity, and industrial relevance of maleimide-based annulation strategies. Additionally, we discuss emerging trends and future directions in maleimide chemistry, exploring opportunities for novel reaction pathways and broader applications in synthetic biology and materials science.

Herein, we report a mild, efficient, and rapid approach for the preparation of CF₃-phenanthridones through a cross-conjugated vinylogous [4 + 2] benzannulation of easily accessible 4-methyl-3-trifluoroacetylquinolones and nitro-olefins. The present transformation is superior to previous approaches for obtaining CF₃-phenanthridones, in that it proceeds exclusively with the assistance of a simple base, eliminating the need for transition metal catalysts or oxidants. The strong electron-withdrawing nature of the CF₃-group present in the quinolone moiety promotes the formation of a reactive cross-conjugated vinylogous enolate.

Diabetes poses a significant global health challenge, driving the search for effective management strategies. In the past years, α-amylase inhibitors have emerged as promising candidates for regulating blood sugar levels. In this concern, we have synthesized a series of novel 3-methyl-2-aroylthiazolo[3',2':2,3][1,2,4]triazino[5,6-b]indole derivatives via the regioselective reaction of 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole-3-thione and 1,3-diketones in the presence of NBS under solvent-free conditions. Subsequently, the inhibitory potential of the newly synthesized 3-methyl-2-aroylthiazolo[3',2':2,3][1,2,4]triazino[5,6-b]indole derivatives was assessed against the α-amylase enzyme to probe their antidiabetic properties. In vitro studies revealed moderate to excellent α-amylase inhibitory activity, with IC₅₀ values ranging from 16.14 ± 0.41 to 27.69 ± 0.58 μg ml^-1. Furthermore, SAR analysis showed that compounds containing halogen groups exhibited superior inhibition potential, surpassing the standard drug Acarbose (IC₅₀ = 18.64 ± 0.42 μg ml^-1), particularly derivatives substituted with 4-fluoro and 2,4-dichloro groups, with IC₅₀ values of 16.14 ± 0.41 μg ml^-1 and 17.21 ± 0.15 μg ml^-1, respectively. Additionally, molecular docking unveiled the binding modes of ligands with the active site of A. oryzae α-amylase. Encouragingly, the theoretical analyses closely mirrored the experimental findings, further underlining the promise of these synthetic molecules as potent α-amylase inhibitors.

A convenient method to access benzo-fused-γ-sultams via alkyl radical induced cyclization of vinyl sulfonamides is presented. A wide range of carboxylic acids including sterically hindered adamantanes participated as alkyl donors in this Ag(I)-catalyzed decarboxylative alkylation. The reaction utilizes readily available starting materials and demonstrates a broad substrate scope.

An azine-based, non-palindromic, neutral NNN-pincer ligand was synthesised in a single step with an yield of 85%. The palladation of the ligand, using Pd(OAc)₂, was performed in acetonitrile at room temperature to obtain the pincer complex in 88% yield through a simple, cost-effective, and straightforward synthetic procedure. The structure of the complex was confirmed by ¹H NMR, ¹³C NMR, FT-IR, and mass spectrometry. The variable temperature NMR spectra revealed the stability of the complex even at higher temperatures, a characteristic feature of pincer complexes. The generated complex proved to be a versatile catalyst for Acceptorless Dehydrogenative Coupling (ADC) to synthesize N-heterocycles: (i) 1,2-disubstituted benzimidazoles, (ii) 2-phenylquinolines, (iii) 2-phenylquinoxalines and (iv) 2-phenylquinazolinones. Since the side products of the reactions are H₂O and H₂ gas, the catalysis can be considered as a green catalytic process. Quantum chemical calculations indicated the participation of a possible nitrene-imide conversion process during the Metal-Ligand Cooperation (MLC) in ADC reactions.

We report a novel class of azophotoswitches incorporating various five-membered heteroaryl units such as thiazole, isothiazole, thiadiazole, and isothiadiazole. These azophotoswitches were developed through an initial screening of 24 compounds using DFT calculations to identify those with the wavelength of maximum absorption (λ_max) at a long wavelength. Subsequently, eight selected azophotoswitches were synthesized. Compounds containing both thiazole and isothiazole moieties showed relatively long λ_max compared to the other synthesized compounds. These azophotoswitches exhibited reversible isomerization under visible light irradiation at 430 nm, 450 nm, 470 nm (trans to cis) and 525 nm (cis to trans). Analysis of the X-ray crystal structures of the cis isomer of phenylazo[1,3,4-thiadiazole] exhibited a unique orthogonal geometry.

Organosilicon compounds have attracted considerable attention because of their special biological activities. Direct difunctionalization of unsaturated hydrocarbons with organosilicon reagents for the efficient construction of synthetically valuable silicon-functionalized compounds are featured with a high step and atom economy, which could form carbon-silicon/carbon-carbon bonds or carbon-silicon/carbon-hetero bonds in one step. This review summarizes the recent advances on this topic based on different unsaturated hydrocarbons along with typical examples and mechanisms.

Construction of a chiral methanamine unit at the C3 position of pyrrole is highly desirable; nevertheless, it remains challenging due to its intrinsic electronic properties. Herein, we present an operationally straightforward and direct asymmetric approach for accessing α-(3-pyrrolyl)methanamines under benign organocatalytic conditions for the first time. The one-pot transformation proceeds smoothly through an amine-catalyzed direct Mannich reaction of succinaldehyde with various endo-cyclic imines, followed by a Paal-Knorr cyclization with a primary amine. Several N-H/alkyl/Ar α-(3-pyrrolyl)methanamines with an aza-tetrasubstituted center have been synthesized with good yields and excellent enantioselectivity.

We herein report reliable evidence that λ⁵-oxazaphosphetane species are a key intermediate in the transformation of CO₂ and isocyanates through their reaction with N-borane-substituted cyclic phosphine imides (BCPIs). We have isolated and fully characterized several λ⁵-oxazaphosphetane species prepared via formal [2 + 2] cycloaddition reactions between BCPIs and CO₂ or isocyanates. The transformation of these λ⁵-oxazaphosphetanes via retro-ring opening reaction afforded an isocyanate and a carbodiimide from the CO₂- and isocyanate-derived λ⁵-oxazaphosphetanes.

We report a sortase-based site-specific antibody-drug conjugation strategy, which involves an affinity peptide-directed acyl transfer reaction and sortase-mediated peptide ligation. Through the affinity peptide-mediated acyl transfer reaction, an LPXTG-containing peptide is conjugated to a specific Lys side chain of an antibody. Under the assistance of sortase, a protein drug bearing a GG motif reacts specifically with the LPXTG moiety to produce an antibody-drug conjugate. Our strategy for antibody conjugation can be applied not only to chemically synthesized drugs, but also to biologically expressed proteins, and will provide a new sortase-based strategy for the preparation of antibody-drug conjugates.