A deconstructive oxygenation of unstrained primary cycloalkanamines has been developed for the first time using an auto‐oxidative aromatization promoted C(sp3)−C(sp3) bond cleavage strategy. This metal‐free method involves the substitution reaction of cycloalkanamines with hydrazonyl chlorides and subsequent auto‐oxidative annulation to in situ generate pre‐aromatics, followed by N‐radical‐promoted ring‐opening and further oxygenation by 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) and m‐cholorperoxybenzoic acid (mCPBA). Consequently, a series of 1,2,4‐triazole‐containing acyclic carbonyl compounds were efficiently produced. This protocol features a one‐pot operation, mild reaction conditions, high regioselectivity and ring‐opening efficiency, broad substrate scope, and is compatible with alkaloids, osamines, and peptides, as well as steroids.
Background
Dopamine and dopamine receptor D1 (DRD1), a member of the dopamine receptor family, have been indicated to play important roles in cancer progression, but dopamine secretion in hepatocellular carcinoma (HCC) and the effects of DRD1 on HCC remain unclear. This study was designed to explore the contribution of the dopaminergic system to HCC and determine the relationship between DRD1 and prognosis in HCC patients.
Methods
The dopamine metabolic system was monitored using enzyme‐linked immunosorbent assays (ELISAs). The expression of DRD1 was detected by microarray analysis, immunohistochemistry (IHC), and quantitative real‐time PCR (qRT‐PCR). Stable DRD1 knockout and overexpression cell lines were established for investigation. Transwell, colony formation, and Cell Counting Kit 8 (CCK8) assays were performed to assess the malignant behaviors of cancer cells. The cAMP/PI3K/AKT/ cAMP response element‐binding (CREB) signaling pathway was evaluated by Western blot. This pathway, which is agitated by DRD1 in striatal neurons, had been proven to participate in tumor progression. Xenograft HCC tumors were generated for in vivo experiments.
Results
Dopamine secretion increased locally in HCC due to an imbalance in dopamine metabolism, including the upregulation of dopa decarboxylase (DDC) and the downregulation of monoamine oxidase A (MAOA). Dopamine promoted the proliferation and metastasis of HCC. DRD1 was highly expressed in HCC tissues and positive DRD1 expression was related to a poor prognosis in HCC patients. The upregulation of DRD1 agitated malignant activities, including proliferation and metastasis in HCC by regulating the cAMP/PI3K/AKT/CREB pathway, and the downregulation of DRD1 had opposing effects. The effects of dopamine on HCC was reversed by depleting DRD1. SCH23390, a selective DRD1 antagonist, inhibited the proliferation and metastasis of HCC cells both in vitro and in vivo.
Conclusion
Dopamine secretion was locally increased in HCC and promoted HCC cell proliferation and metastasis. DRD1 was found to exert positive effects on HCC progression and play a vital role in the dopamine system, and could be a potential therapeutic target and prognostic biomarker for HCC.
In this work, we
synthesized a series of TiO2 species
enclosed with different terminated facets and investigated the catalytic
performance on glycerol oxidation catalysts over Au1Pt3/TiO2 under base-free conditions. To our surprise,
the Au1Pt3/TiO2 catalyst presented
a support-facet-dependent catalytic performance. Different TiO2 crystal planes apparently affect the oxidation product distribution,
especially the selectivity of glyceraldehyde and glyceric acid, but
have inconspicuous influence on the activity of glycerol oxidation.
Primarily, the coordination unsaturated sites O2c-Ti5c-O2c of the (001) facet highly dissociated the
CO bond of aldehyde group in a bidentate form, as characterized
by in situ CO2 and formaldehyde Fourier transform infrared
spectroscopy. In another aspect, Auδ+ species were
generated on the interface between AuPt nanoparticles and the (001)
facet of TiO2 due to the strong interaction, which facilities
the insertion of oxygen species during the process of oxidation to
glyceric acid. With the aid of bidentate intermediates and Ti5c-O2c-Auδ+ active sites, the ability
of further oxidation of glyceraldehyde is enhanced due to the decreased
active energy of glyceraldehyde over Au1Pt3/TiO2-001, as revealed by the kinetic studies of glyceraldehyde
oxidation. These findings provide an alternative perspective and feasible
approach to manipulate the product distribution in multistep continuous
oxidation reactions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.