Organic & Biomolecular Chemistry最新文献

The first biomimetic and concise racemic total syntheses of renifolin F and antiarone K, accomplished in 8 and 7 linear steps, respectively, are presented in this article. Our synthetic approach commences with substituted aldehydes to produce prenylated aldol products followed by ene-type intramolecular cyclization affording a five-member core ring. This key step mediated by InCl₃·4H₂O is a novel procedure first utilized in prenylated systems which directly culminates mainly into tertiary alcohols.

Herein, a novel transition-metal-free thiol-based donor–acceptor organophotocatalyst-assisted, singlet-oxygen-mediated tandem oxidative cyclization for the synthesis of substituted oxazoles in moderate-to-good yields is described. The developed method demonstrates applicability for the synthesis of various substituted quinoxalines in good-to-excellent yields. The metal-free methodology shows a practical route for the synthesis of oxazole and quinoxaline derivatives, which are privileged moieties prevalent in various biologically active compounds and natural products. To the best of our knowledge, both the thiol photocatalyst and synthesis of oxazoles by visible-light irradiation are reported for the first time.

Among the fastest-growing bio-pharmaceuticals, therapeutic antibodies have achieved unprecedented success in treating various diseases. Though powerful, issues such as inefficacy or acquired resistance are waiting to be addressed to benefit more patients with improved therapeutic outcomes. In addition to in vivo distribution, the cellular spatiotemporal information including the antibody–antigen interaction and subsequent internalization is found to be important for the therapeutic effects. To better understand the cellular fate of therapeutic antibodies, especially the cellular internalization process, we employed a pH-sensitive linker to attach a red-emissive AIEgen onto the antibody. The resulting antibody conjugate will undergo AIEgen release to liberate brilliant fluorescence inside acidic endo/lysosomes, allowing wash-free visualization of the internalization process and facilitating the evaluation of antibody–drug efficacy.

A photoredox/copper-catalyzed 1,4-difunctionalization of 1,3-enynes with readily available difluoroalkylating reagents and TMSCN was developed. This reaction proceeded at mild conditions, affording the corresponding difluoroalkylated allenes in good yields with high functional-group tolerance and excellent regioselectivity.

The first total synthesis and absolute configuration assignment of asperilactone B (I) have been accomplished. Additionally, a revision of the absolute stereochemistry of asperilactone C has been done. The first total synthesis of the opposite enantiomer of asperilactone B (ent-I) has also been achieved, as well as that of C-7 epimers of both asperilactones B (8) and C (9).

A straightforward and efficient methodology has been employed for the synthesis of a diverse set of base-modified fluorescent nucleoside conjugates via Cu(i)-catalysed cycloaddition reaction of 5-ethynyl-2′,3′,5′-tri-O-acetyluridine/3′,5′-di-O-acetyl-2′-deoxyuridine with 4-(azidomethyl)-N⁹-(4′-aryl)-9,10-dihydro-2H,8H-chromeno[8,7-e][1,3]oxazin-2-ones in ^tBuOH to afford the desired 1,2,3-triazoles in 92–95% yields. Treatment with NaOMe/MeOH resulted in the final deprotected nucleoside analogues. The synthesized 1,2,3-triazoles demonstrated a significant emission spectrum, featuring two robust bands in the region from 350–500 nm (with excitation at 300 nm) in fluorescence studies. Photophysical investigations revealed a dual-emissive band with high fluorescence intensity, excellent Stokes shift (140–164 nm) and superior quantum yields (0.068–0.350). Furthermore, the electronic structures of the synthesized triazoles have been further verified by DFT studies. Structural characterization of all synthesized compounds was carried out using various analytical techniques, including IR, ¹H-NMR, ¹³C-NMR, ¹H–¹H COSY, ¹H–¹³C HETCOR experiments, and HRMS measurements. The dual-emissive nature of these nucleosides would be a significant contribution to nucleoside chemistry as there are limited literature reports on the same.

We report herein a synthesis of allylic phosphoramidates from alkenes by selenium-catalyzed allylic C–H derivatization. This method features mild conditions, broad substrate scope, and high functional group tolerance, enabling late-stage modification of a number of complex substrates. In addition, this protocol was applied to modify caryophyllene and produced a photoaffinity probe capable of proteomic target labeling in live HeLa cells.

Development of biocompatible nanomaterials with mitochondria-targeting and multimodal therapeutic activities is important for cancer treatment. Herein, we designed and synthesized a multifunctional pyrrole-based nanomaterial with photothermal effects and mitochondria-targeting properties from polypyrrole and the pro-apoptotic peptide KLA. Different from traditional strategies for the preparation of PPy nanoparticles, we innovatively used the KLA peptide as the template and CuCl₂ as the catalyst to trigger the oxidative polymerization of pyrrole for PPy-KLA-Cu nanoparticle formation. Besides, due to the presence of mixed-valence Cu(i)/Cu(ii) states, PPy-KLA-Cu nanoparticles also exhibited multienzyme-like activities, such as peroxidase, ascorbate oxidase and glutathione peroxidase activities, which can be exploited to elevate the intracellular ROS level and simultaneously consume GSH in cancer cells. More importantly, the heat generated by PPy-KLA-Cu nanoparticles from NIR irradiation could enhance the nanozymatic activities for ROS elevation and increase the KLA-induced anticancer activity via mitochondrial dysfunction, realizing multimodal treatment of cancer cells with improved therapeutic efficacy.

Visible light-induced aza-6π electrocyclization was developed for the synthesis of aza-arenes from nitroarenes with diverse aldehydes. This protocol allows the reduction of nitroarenes by B₂nep₂ and subsequent 6π-electrocyclization of the in situ formed imine under visible light. An array of 6- and multi-substituted phenanthridines were constructed in moderate to good yields under purple LEDs at room temperature. A wide scope of substrates with diverse functional groups were well tolerated. In addition, the synthetic utility of this methodology was further demonstrated in the late-stage functionalization of celecoxib.

Benzylic C–H bonds can be converted into numerous functional groups, often by mechanisms that involve hydrogen atom transfer as the key bond breaking step. The abstracting species is most often an electrophilic radical, which makes these reactions best suited to electron-rich C–H bonds to achieve appropriate polarity matching. Thus, electron deficient systems such as pyridine and pyrimidine are relatively unreactive, and therefore underrepresented in substrate scopes. In this report, we describe a new method for heterobenzylic hydroxylation—essentially an unknown reaction in the case of pyrimidines—that makes use of an iodine(iii) reagent to afford very high selectivity towards electron-deficient azaheterocycles in substrates with more than one reactive position and prevents over-oxidation to carbonyl products. The identification of key reaction byproducts supports a mechanism that involves radical coupling in the bond forming step.