Organic & Biomolecular Chemistry最新文献

Herein we present the first total synthesis of the tetrasaccharide repeating units from Pseudomonas chlororaphis subsp. aureofaciens UCM B-111, achieved through a stepwise assembly of the core tetrasaccharide structure. The tetrasaccharide units consist of two D-glucosamine units at the terminals, with D-galactosamine and D-quinovosamine rare sugar unit linked by two α- and two β-glycosidic bonds. The total synthesis of 1 and 2 was accomplished via the longest linear sequences of 23 and 22 steps with an overall yield of 2.9% and 3.8%, respectively.

A metal-free photocatalytic method for the synthesis of silylated thioflavones and benzothiophenes has been established through cascade silylation/cyclization of alkynes/alkynones with hydrosilanes. This transformation features mild reaction conditions, excellent functional group compatibility, and broad substrate scope. Moreover, this method can be readily applied to the late-stage silylation of structurally complex bioactive molecules, thus offering potential applications for pharmaceutical research. Mechanistic investigations indicate that this reaction proceeds through a radical pathway.

Research into the epimerization of piperidine-2-ones is exceedingly scarce. Blue light can induce epimerization of piperidine-2-ones, but this transformation necessitates the use of a blue LED and an iridium photocatalyst. We describe here the epimerization reactions of 2-piperidone-substituted pyridinium salts and 1,4,5,6-tetrahydropyridines in DMSO. The method is easy to perform and requires no catalysts or additional bases. An epimerization mechanism was proposed for each of these cases, and density functional theory (DFT) calculations were performed. With the aid of the noncovalent interaction (NCI) index, we were able to identify weak interactions within the molecule of a thermodynamically favorable epimer and compare them with those of a less thermodynamically favorable one.

A Brønsted acid-catalyzed (3 + 2) cycloaddition of 2-indolylmethanols with o-alkynylnaphthols has been developed, leading to the efficient synthesis of cyclopenta[b]indoles with structural diversity in generally high yields. This study presents the first application of alkynes as 2C reaction partners in cycloadditions of 2-indolylmethanols. Furthermore, a chiral resolution strategy was developed using (R)-(-)-O-formylmandeloyl chloride as a resolution reagent to obtain optically pure cyclopenta[b]indole atropisomers from racemic substrates. Additionally, a catalytic asymmetric version of this (3 + 2) cycloaddition has been preliminarily explored, which disclosed the potential of the reaction for the enantioselective synthesis of axially chiral cyclopenta[b]indoles. This work not only offers a practical approach for the synthesis of cyclopenta[b]indoles bearing indole-fused five-membered rings but also expands the scope of indolylmethanol chemistry.

A metal- and oxidant-free photocatalytic cascade reaction has been developed for the divergent synthesis of sulfonamidylated chroman-4-ones. This visible-light-driven protocol employs readily available o-(allyloxy)arylaldehydes and N-sulfonylaminopyridinium salts as feedstocks. A sulfonamidyl radical-triggered addition-cyclization sequence enables the one-step assembly of a new heterocyclic ring with the concomitant formation of C-N and C-C bonds. The mild conditions afford the desired products in moderate to good yields, obviating the need for noble-metal catalysts or external oxidants. This sustainable strategy not only enriches the structural diversity of chroman-4-one scaffolds but also paves the way for constructing bioactive compound libraries.

This article reports one-pot synthesis of aroylmethyl-conjugated pyrazolo[5,1-a]isoindoles via t-butyl carbazate-mediated double Michael addition/cyclocondensation of diaroyl benzothiepine-1,1-dioxides. In the reaction process, the seven-membered ring is converted into a bicyclo[5.5] core skeleton by the formation of two carbon-nitrogen single bonds and one carbon-nitrogen double bond under mild conditions. The related plausible mechanism is also discussed here.

The inexpensive copper(II) bromide-catalyzed cross-dehydrogenative coupling/Kornblum oxidation/formal decarbonylation of N-substituted/unsubstituted quinoxalinones in DMSO is reported. It has offered a new technique for the cleavage of C(CO)-C(CO) bonds under base- and ligand-free conditions, allowing for the direct synthesis of a diverse range of C3-acylated quinoxalinones. This persulfate-peroxide-free catalytic method provides good yields, a broad substrate scope, and good tolerance to various functionalities.

Cyclin-dependent kinase 6 (CDK6) is a key therapeutic target in breast cancer, and its abnormal activation, together with Cyclin D3, promotes uncontrolled cell proliferation. Traditional CDK4/6 inhibitors only inhibit kinase activity without degrading the target protein, which readily causes drug resistance. In this study, we designed and synthesized a series of photo-controlled CDK6 degraders (LL1-LL7) using palbociclib as the core pharmacophore and linking photosensitizers to generate reactive oxygen species (ROS) under light. Among them, LL5 showed the best CDK6 degradation and antiproliferative activity. LL5 produces ROS via a Type II mechanism under 450 ± 25 nm LED light and elevates intracellular ROS in T47D cells. Western blot revealed that LL5 barely affected CDK6 and Cyclin D3 in the dark but markedly degraded both proteins after 15 min of irradiation, owing to ROS-mediated structural damage and the proximity effect between the two proteins. Functional assays showed that light irradiation significantly enhanced the antiproliferative activity of LL5. It displayed good selectivity between cancer and normal breast epithelial cells and induced G0/G1 arrest and apoptosis in T47D cells under light. In conclusion, LL5 acts as a photo-controlled degrader that co-degrades CDK6 and Cyclin D3 through light-triggered ROS and proximity effects, offering a promising new strategy for breast cancer treatment.

Herein, we describe a metal-free N-acylation of sulfoximines mediated by an N-chlorophthalimide/triphenylphosphine (NCP/PPh₃) system. The transformation proceeds under mild reaction conditions and provides efficient access to structurally diverse N-acyl sulfoximines in good yields. The protocol exhibits a broad substrate scope, excellent functional-group tolerance, and is readily scalable. Notably, the protocol applies to aromatic, benzylic, and α-keto carboxylic acids, providing straightforward access to a wide range of N-acyl sulfoximines of potential biological relevance.

The first total synthesis of kasichelins A and B was accomplished in a concise manner via a longest linear sequence of seven steps with 25% and 18% overall yields, respectively. The synthetic route featured a judicious choice of protecting groups, a molybdenum-promoted dehydrative cyclization for construction of the dihydrooxazole core, and a convergent fragment assembly strategy to forge the complete molecular scaffold.