Organic & Biomolecular Chemistry最新文献

α-Substituted vinyl P(V)-molecules are important scaffolds with wide applications. Although several synthetic methods have been developed, few of them are equally feasible for the general synthesis of different types of P(V)-structures. Herein, we developed a benign tandem Arbuzov-Perkow reaction between the readily available chloroacetyl chloride and various P(III)-reagents, delivering the corresponding enol bisphosphorus compounds in high yields. The subsequent Negishi coupling reaction via selective cleavage of the P(O)O-C(sp²) bond enabled efficient introduction of a (hetero)aryl or a (cyclo)alkyl group onto the P-adjacent C(sp²)-carbon, affording diverse α-substituted terminal alkenyl phosphonates, phosphinates, and phosphine oxides with generally good to excellent yields, respectively.

Herein, we describe an efficient approach for the synthesis of SCF₃- and SCN-functionalized polycyclic dihydroisoquinolino[1,2-b]quinazolinones through radical-mediated thio-functionalization of allylic alkenes followed by intramolecular cyclization. The transformation proceeds through sulfur-radical-triggered C-S and C-C bond formation, providing an efficient route to sulfur- and fluorine-enriched polycyclic quinazolinones. Moreover, this strategy offers high atom economy, operational simplicity, and broad substrate compatibility.

DBU-mediated, facile and divergent [3 + 3] benzannulation reactions of aurones and 1,3-bisnucleophiles afforded substituted dibenzofurans. Nucleophiles possessing at least one arylsulfone group reacted via an elimination pathway whereas diethyl glutaconate reacted via an aerial oxidation pathway. The aurone assembly and ensuing benzannulation could also be carried out as a one-pot, three-component reaction.

Herein, we report an efficient electrochemical redox condensation strategy for the construction of diverse 2-substituted benzoxazole derivatives from readily available o-nitrophenols and alcohols in an undivided cell. This electrocatalytic reaction makes full use of both anodic oxidation and cathodic reduction, obviating the requirement for metal catalysts or chemical oxidants. Mechanistic investigations including control experiments and cyclic voltammetry suggest an intermolecular electrochemical redox/cyclization pathway.

A one-pot, three-component 1,3-dipolar cycloaddition of maleimides with azomethine ylides generated in situ from pyrazolediones and prolines has been developed, and a series of novel pharmaceutically interesting spiro-pyrazolone-pyrrolizines containing succinimides was obtained in moderate to excellent yields with poor to excellent diastereoselectivities.

We report an efficient electrocatalytic selenocyclization strategy that enables the synthesis of selenium-containing oxazolidinones from diselenides and N-Boc allylamines. This oxidant-free method employs electrons as a clean redox agent in an undivided cell, demonstrating broad substrate scope, gram-scale applicability, and successful extension to other selenium heterocycles. Mechanistic investigations have elucidated a distinct pathway from conventional oxidation, involving a hybrid radical/cationic process. This insight not only deepens our mechanistic understanding but also showcases the significant potential of electrosynthesis for sustainable heterocycle construction.

An electrochemical α-alkenylation of nitriles was developed in an undivided cell under base-free conditions. A wide range of nitriles and aldehydes were effectively converted into the corresponding α-alkenylated derivatives with high yields by virtue of this method. The reaction features broad substrate scope, metal-free and chemical oxidant-free conditions, and scalability.

A ruthenium-catalyzed method has been developed for the direct C2-H selenylation of (benz)imidazole, enabling efficient selenium incorporation at the C2 position to yield diverse selenylated derivatives. This system operates under mild conditions with a broad substrate scope, excellent functional group tolerance, and high regioselectivity. Notably, diaryl disulfides were also successfully employed under identical conditions.

Fungi are well known to biosynthesize structurally complex secondary metabolites (SMs) with diverse bioactivities. These fungal SMs are frequently produced by biosynthetic gene clusters (BGCs). Linking SMs to their BGCs is key to understanding their chemical and biological functions. Reasoning that structural similarity of SMs arises from similarities in the genes involved in their biosynthesis, we developed an integrative approach that leverages known SM-BGC pairs to infer links between detected SMs and genome-predicted BGC regions in fungi. As proof of concept, we structurally characterized 60 metabolites from metabolomic data of 16 strains of the filamentous fungus Aspergillus fischeri. Our approach assigned 22 to known SM-BGC pairs and proposed specific links to BGCs and genetic pathways for the remaining 38 metabolites. These results suggest that coupling chemical structure similarity and genomic sequence similarity is a straightforward and high-throughput approach for linking fungal SMs to their BGCs.

The biological functions of the molecular chaperone Hsp90 are driven by pronounced conformational dynamics, yet the local structural features of these dynamics under phyisological conditions remain incompletely understood. Here, we systematically assessed the solvent accessibility of native cysteine residues in wild-type human Hsp90β in the apo state using a panel of thiol-reactive chemical probes with distinct physicochemical properties. Mass spectrometry identifies Cys366 as the most preferentially modified native cysteine in solution. Notably, the chemical accessibility of Cys366 is not measurably affected by nucleotide binding or hydrolysis, indicating that nucleotide-induced shifts in the Hsp90β conformational ensemble do not significantly impact the local environment close to this site. These results highlight the value of a practical framework for selecting and interpreting cysteine labeling sites in Hsp90 and related chaperone systems and also indicate a strategy for probing local accessibility of structural segments in conformationally dynamic protein complexes.