Synthetic Studies on Small Molecule Natural Products with Neurotrophic Activity

Fukuyama, Yoshiyasu

doi:10.1248/yakushi.21-00201

Cited by 4 publications

(2 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These metabolic reactions mainly include the major phase I reactions of oxidation, reduction, and internal hydrolysis, and the major phase II reactions of glucuronidation, sulfation, methylation, acetylcysteine conjugation and glutathione binding, and their composite reactions. Among them, many fat-soluble metabolites were found, which were beneficial to exerting efficacy through the blood-brain barrier ( Fukuyama, 2022 ; Trushina et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Serial five-membered lactone ring ions in the treatment of Alzheimer’s diseases-comprehensive profiling of arctigenin metabolites and network analysis

Lan

Wang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Arctigenin is a phenylpropanoid dibenzylbutyro lactone lignan compound with multiple biological functions. Previous studies have shown that arctigenin have neuroprotective effects in Alzheimer’s disease (AD) models both in vivo and in vitro; however, its metabolism in vivo has not been studied. Most traditional analytical methods only partially characterize drug metabolite prototypes, so there is an urgent need for a research strategy that can fully characterize drug metabolites. In the present study, ions fishing with a serial five-membered lactone ring as a fishhook strategy based on ultrahigh-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was utilised to characterise the metabolism of arctigenin, and the establishment of this strategy also solved the challenge of creating a comprehensive metabolic profile of neolignan. Based on the proposed strategy, a total of 105 metabolites were detected and characterised, 76 metabolites of which were found in rats and 49 metabolites in liver microsomes. These metabolites were postulated to be produced through oxidation, reduction, hydrolysis, and complex reactions. Subsequently, network pharmacology was utilized to elucidate the mechanism of arctigenin and its main metabolites against Alzheimer’s disease, screening 381 potential targets and 20 major signaling pathways. The study on the comprehensive metabolism of arctigenin provides a holistic metabolic profile, which will help to better understand the mechanism of arctigenin in the treatment of Alzheimer’s disease (AD) and also provide a basis for the safe administration of arctigenin.

show abstract

Section: Discussionmentioning

confidence: 99%

Serial five-membered lactone ring ions in the treatment of Alzheimer’s diseases-comprehensive profiling of arctigenin metabolites and network analysis

Lan

Wang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Axially chiral compounds, especially the axially chiral biaryl atropisomers, have obtained considerable attention from organic chemists and medicinal chemists due to their widespread presence in biologically active molecules such as Mastigophorene A, Korupensamine A, and Steganacin (Scheme ). In addition, axially chiral biaryl atropisomers find wide-ranging utilities in functional materials, ,,− for example, fluorescent sensor and rotary molecular motor, or they are used as privileged chiral ligands (e.g., BINAP, BINOL) − and catalysts for asymmetric synthesis. , Owing to the importance of these scaffolds, great progress has been achieved in the synthesis of axially chiral biaryl compounds over the past decades.…”

Section: Synthetic Applications Of Cyclic Aryliodoniumsmentioning

confidence: 99%

Recent Progress in Cyclic Aryliodonium Chemistry: Syntheses and Applications

et al. 2023

View full text Add to dashboard Cite

Hypervalent aryliodoumiums are intensively investigated as arylating agents. They are excellent surrogates to aryl halides, and moreover they exhibit better reactivity, which allows the corresponding arylation reactions to be performed under mild conditions. In the past decades, acyclic aryliodoniums are widely explored as arylation agents. However, the unmet need for acyclic aryliodoniums is the improvement of their notoriously low reaction economy because the coproduced aryl iodides during the arylation are often wasted. Cyclic aryliodoniums have their intrinsic advantage in terms of reaction economy, and they have started to receive considerable attention due to their valuable synthetic applications to initiate cascade reactions, which can enable the construction of complex structures, including polycycles with potential pharmaceutical and functional properties. Here, we are summarizing the recent advances made in the research field of cyclic aryliodoniums, including the nascent design of aryliodonium species and their synthetic applications. First, the general preparation of typical diphenyl iodoniums is described, followed by the construction of heterocyclic iodoniums and monoaryl iodoniums. Then, the initiated arylations coupled with subsequent domino reactions are summarized to construct polycycles. Meanwhile, the advances in cyclic aryliodoniums for building biaryls including axial atropisomers are discussed in a systematic manner. Finally, a very recent advance of cyclic aryliodoniums employed as halogen-bonding organocatalysts is described.

show abstract