The 1,2-dicarbonyl motif is vital to biomolecules, especially natural products and pharmaceuticals. Conventionally, 1,2-dicarbonyl compounds are prepared via an α-keto acyl chloride. Based on the methods used in nature, a transition-metal-free approach for the synthesis of an α-ketothioester reagent via the combination of an α-hydroxyl ketone, elemental sulfur and a benzyl halide is reported. Mechanistic studies demonstrate that the trisulfur radical anion and the α-carbon radical of the α-hydroxy ketone are involved in this transformation. The dicarbonylation of a broad range of amines and amino acids, and importantly, cross couplings with aryl borates to construct dicarbonyl-carbon bonds are realized under mild conditions by employing this stable and convenient α-ketothioester as a 1,2-dicarbonyl reagent. The dicarbonyl-containing drug indibulin and the natural product polyandrocarpamide C, which possess multiple heteroatoms and active hydrogen functional groups, can be efficiently prepared using the designed 1,2-dicarbonyl reagent.

Copper-catalyzed, aerobic, oxidative, C3-dicarbonylation of indoles has been realizedd irectly from a-hydroxyketones,w hich serve as an efficient dicarbonylative reagent under mild conditions. The method is widely compatibility with various functional groups, offering as traightforward means to produce differenth eterocyclesubstituted quinoxalines in excellent yields. These diverse fluorescent quinoxalines exhibited photophysical properties and solvatochromism in certain rules. Based on control experiments, ap lausible reaction mechanism was proposed.Scheme1.1,2-Dionemotif and important quinoxaline derivatives.Scheme2.Oxygenationand green oxidation of a-hydroxyketones controlled by reaction conditions.

Up to 30% of patients with metastatic castration‐resistant prostate cancer (CRPC) patients carry altered DNA damage response genes, enabling the use of poly adenosine diphosphate–ribose polymerase (PARP) inhibitors in advanced CRPC. The proto‐oncogene mesenchymal–epithelial transition (MET) is crucial in the migration, proliferation, and invasion of tumour cells. Aberrant expression of MET and its ligand hepatocyte growth factor is associated with drug resistance in cancer therapy. Here, we found that MET was highly expressed in human CRPC tissues and overexpressed in DU145 and PC3 cells in a drug concentration‐dependent manner and is closely related to sensitivity to PARP inhibitors. Combining the PARP inhibitor olaparib with the MET inhibitor crizotinib synergistically inhibited CRPC cell growth both in vivo and in vitro. Further analysis of the underlying molecular mechanism underlying the MET suppression‐induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib‐induced antitumour effect in DU145 and PC3 cells. In conclusion, we demonstrated that MET inhibition enhances sensitivity of CRPC to PARP inhibitors by suppressing the ATM/ATR and PI3K/AKT pathways and provides a novel, targeted therapy regimen for CRPC.

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High levels of Basic Transcription Factor 3 (BTF3) have been associated with prostate cancer. However, the mechanisms underlying the role of BTF3 as an oncogenic transcription factor in prostate tumorigenesis have not been explored. Herein, we report that BTF3 confers oncogenic activity in prostate cancer cells. Mechanistically, while both BTF3 splicing isoforms (BTF3a and BTF3b) promote cell growth, BTF3b, but not BTF3a, regulates the transcriptional expression of the genes encoding the subunits of Replication Factor C (RFC) family that is involved in DNA replication and damage repair processes. BTF3 knockdown results in decreased expression of RFC genes, and consequently attenuated DNA replication, deficient DNA damage repair, and increased G2/M arrest. Furthermore, knockdown of the RFC3 subunit diminishes the growth advantage and DNA damage repair capability conferred by ectopic overexpression of BTF3b. Importantly, we show that enforced BTF3 overexpression in prostate cancer cells induces substantial accumulation of cisplatin-DNA adducts and render the cells more sensitive to cisplatin treatment both in vitro and in vivo. These findings provide novel insights into the role of BTF3 as an oncogenic transcription factor in prostate cancer and suggest that BTF3 expression levels may serve as a potential biomarker to predict cisplatin treatment response.