Organic & Biomolecular Chemistry最新文献

A visible-light-induced C-3 alkylation of quinoxalin-2(1H)-ones with N,N,N′,N′-tetraalkylethylenediamine was achieved without an external photocatalyst. The mechanism showed that quinoxalin-2(1H)-ones could act as photocatalysts. The accessibility of the reagents and the green and mild reaction conditions made this protocol an alternative method to access C-3 alkylated quinoxalin-2(1H)-ones.

A mild, scalable, and high-yielding visible-light-promoted C–S cross-coupling between alkyl thiol derivatives and (hetero)aryl halides without the need for metals, ligands, or photocatalysts is reported, offering advantages over traditional C–S bond forming strategies. The formation of an electron donor–acceptor (EDA) complex is supported by experimental and computational mechanistic studies, which undergoes visible-light-induced charge transfer to initiate C–S bond formation in the absence of a photoredox catalyst.

This study introduces a silver-catalyzed method for the efficient and regioselective synthesis of pyrano heterocycles, utilizing readily available alcohols and water as nucleophiles. The method demonstrates high efficiency, delivering excellent yields and selectivity, and is scalable to gram quantities while maintaining broad functional group tolerance. Notably, the synthesized pyrano[3,4-c]quinolines were successfully transformed into diverse samoquasine A derivatives, underscoring the method's applicability in natural product synthesis. This work represents a significant advancement in pyrano heterocycle synthesis, offering a practical route to valuable compounds with potential applications in pharmaceutical and chemical research.

Here, we present for the first time the synthesis of P-stereodefined morpholino phosphorothioate analogs by using a modified 1,3,2-oxathiaphospholane method (OTP method) and provide valuable structural insights into their stereochemistry. N-(2-Thio-4,4-pentamethylene-1,3,2-oxathiaphospholane) derivatives of morpholino-type nucleosides (mU-OTPs) were synthesized, separated into pure P-diastereomers and used to prepare P-stereodefined morpholino dinucleoside 3′,5′-phosphorothioates.

As a special class of alkynes, gem-difluoromethylene alkynes exhibit a variety of fascinating properties due to the presence of the gem-difluoro substitution. This substitution highlights the distinctive fluorine effects in influencing the chemoselectivity of reactions. As a result, chemical scientists have shown great interest and enthusiasm for investigating their reactions. In this review, we briefly summarize recent advances in transition metal-catalysed reactions of gem-difluoromethylene alkynes with multiple reaction pathways. Their mechanistic studies and challenges will be highlighted. The purpose of this review is to provide illustrations of elegant gem-difluoromethylene alkynes and thereby elicit further interest among synthetic chemists in developing innovative transformations of gem-difluoromethylene alkynes.

Benzo[b]thiophene rings are common synthons for the development of novel drugs and materials, and thus, the discovery of facile ways for their functionalization is of value. In this work, a new method for the C3-chlorination of C2-substituted benzothiophene derivatives is described. The chlorine source is sodium hypochlorite pentahydrate (NaOCl·5H₂O), and optimal transformations occur in aqueous acetonitrile at 65–75 °C to provide the corresponding C3-halogenated products in variable yields (30–65%). The reaction occurs in the presence of vinyl and alkyl groups, while the presence of alcohols leads to competing oxidation reactions at the heterobenzylic position. The presence of a carbonyl group at the C2-position inhibited the halogenation reaction, while the use of benzofuran led to a highly exothermic reaction, presumably via the formation of a peroxide intermediate. Reactions carried out at lower temperatures led to side reactions associated with competing oxidative processes. To gain a better understanding of the mechanism of the reaction, DFT calculations were carried out, where the heteroatom enables the formation of a hypochlorous acidium ion that serves to generate a C2–C3 chloronium ion intermediate in a step-wise manner, which in turn leads to the formation of an S-stabilized C2-carbocation that undergoes re-aromatization to the corresponding C3-chlorinated products. To probe potential synthetic applications, a model C3-chloro derivative was coupled with phenylboronic acid using standard Suzuki–Miyaura coupling conditions.

Opantimycin A, a rare antimycin-class antibiotic without the macrolide core, was isolated from Streptomyces sp. RK88-1355 in 2017. In this study, we explored the total synthesis and stereochemical assignment of opantimycin A. The synthesis of all potential diastereomers has been accomplished via traceless Staudinger ligation. A comparison of the spectroscopic data of the synthesized compounds with that reported for the natural product confirmed that the absolute configuration of the natural product was (14S,17R,21R). Two analogous compounds were prepared, where the Dhb ((Z)-dehydrobutyrine) moiety was replaced with Dha (dehydroalanine) or ΔVal moieties, respectively. The inhibitory activities of these synthetic compounds against the production of the anti-inflammatory cytokine IL-6 were evaluated, and two potential candidates for further development as anti-inflammatory agents were identified.

Herein, an efficient, base catalyzed cascade vinylogous Michael/Michael cycloaddition reaction of α-alkylidene succinimides and oxindole-derived pyrazolones has been successfully developed. A variety of highly functionalized cyclopentanes fused with spirooxindoles were obtained in good yields, with excellent diastereoselectivities and exclusive vinylogous site-selectivities. This strategy represents the first example of α-alkylidene succinimides serving as nucleophilic reagents to trigger a vinylogous cascade reaction.

Natural products play a pivotal role in the advancement of state-of-the-art pharmaceuticals. To augment their therapeutic efficacy, structural modifications of these compounds are routinely performed. In this study, we introduce an efficient and environmentally benign electrochemical oxidative method for site-selective direct C–H activation of tanshinone IIA under metal-free, oxidant-free, and base-free conditions. Moderate to excellent yields up to 92% of the desired tanshinone IIA derivatives were obtained with a broad substrate scope. Biological activity assays demonstrate that compounds 2k, 2q and 2w possess superior antitumor efficacy compared to tanshinone IIA.

Four previously undescribed heterodimeric diketopiperazine alkaloids, expansines A–D, were identified from the solid rice medium fermented by Penicillium expansum MA147, along with one new resorcylic acid derivative and five known compounds. Their structures and relative/absolute configurations were elucidated by interpretation of their spectroscopic data, quantum chemical calculations, and chemical conversion. Some obtained compounds were evaluated for the cytotoxicity against a triple-negative breast cancer cell line MDA-MB-231, and expansine C showed an IC₅₀ value of 3.23 μM. In further mechanistic studies, we found that it might act by increasing the expression of ATP-binding cassette transporter A1 and reducing cellular cholesterol levels, suggesting its potential as a novel anti-cancer agent.