To elucidate the mechanism of anti-ferroptosis and examine structural optimization in natural phenolics, cellular and chemical assays were performed with 2′-hydroxy chalcone butein and dihydroflavone (S)-butin. C11-BODIPY staining and flow cytometric assays suggest that butein more effectively inhibits ferroptosis in erastin-treated bone marrow-derived mesenchymal stem cells than (S)-butin. Butein also exhibited higher antioxidant percentages than (S)-butin in five antioxidant assays: linoleic acid emulsion assay, Fe3+-reducing antioxidant power assay, Cu2+-reducing antioxidant power assay, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-trapping assay, and α,α-diphenyl-β-picrylhydrazyl radical (DPPH•)-trapping assay. Their reaction products with DPPH• were further analyzed using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Butein and (S)-butin produced a butein 5,5-dimer (m/z 542, 271, 253, 225, 135, and 91) and a (S)-butin 5′,5′-dimer (m/z 542, 389, 269, 253, and 151), respectively. Interestingly, butein forms a cross dimer with (S)-butin (m/z 542, 523, 433, 419, 415, 406, and 375). Therefore, we conclude that butein and (S)-butin exert anti-ferroptotic action via an antioxidant pathway (especially the hydrogen atom transfer pathway). Following this pathway, butein and (S)-butin yield both self-dimers and cross dimers. Butein displays superior antioxidant or anti-ferroptosis action to (S)-butin. This can be attributed the decrease in π-π conjugation in butein due to saturation of its α,β-double bond and loss of its 2′-hydroxy group upon biocatalytical isomerization.

https://www.mdpi.com/1420-3049/25/3/674/pdf

Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (S)-Butin.

Proanthocyanidins (PACs) are oligomers or polymers composed of units of flavanols. A-type PACs are a subclass of PACs characterized by the presence of at least a double linkage between two consecutive monomers of flavanol. These A-type PACs are found in some fruits and spices and possess potential health benefits as a result of their interesting biological activities, and consequently, their isolation and synthesis have given rise to great interest in the past. This review summarizes the synthetic efforts made to obtain both naturally occurring A-type PACs and their structurally simplified analogues. Most of the synthetic protocols reported involve the addition of a π-nucleophilic molecule over a molecule with two electrophilic carbons, such as a chalcone, a flavylium salt, or a flavanol derivative, among others. Synthesis of A-type PACs remains an issue at a very early stage of development compared to that of PACs with single linkages between monomers (B-type PACs), but the advances that are taking place in the last few years point to a significant development of the subject in the near future.

Synthesis of A-Type Proanthocyanidins and Their Analogues: A Comprehensive Review

Visible-light driven synthesis of polycyclic benzo[d][1,3]oxazocine from 2-aminochalcone.

Halogen (fluorine, chlorine, bromine, iodine) or chalcogen (sulfur, seleno)-containing heterocycles are widely recognized as key building blocks in many natural products and bioactive targets. Catalytic asymmetric halogenation/chalcogenation of carbon-carbon unsaturated bonds via onium ion transformations are efficient methods to obtain diverse chiral heterocyclic backbones. In the past few years, catalytic enantioselective versions of halo/thio/seleno-functionalizations with various halogen and chalcogen electrophiles have experienced constant development. This review highlights those advances in preparing functionalized heterocycles promoted by chiral organocatalysts or metal-based catalysts. 

Recent advances in catalytic asymmetric syntheses of functionalized heterocycles via halogenation/chalcogenation of carbon‐carbon unsaturated bonds

Asymmetric Synthesis of ent-Fissistigmatin C.

A bio-inspired synthesis of hybrid flavonoids from 2-hydroxylchalcone is described. Under the irradiation of 24 W CFL, 2-hydroxychalcone reacts with various nucleophiles to deliver structurally diverse hybrid flavonoids in good to excellent yields in the presence of a catalytic Bronsted acid. Moreover, moderate enantioselectivities could be obtained using a catalytic chiral phosphoric acid via counter anion directed addition. Based on mechanistic studies, the reaction is proposed to proceed via tandem double-bond isomerization/dehydrated cyclization of 2-hydroxychalcone to form a transient flavylium cation, which is in situ captured by nucleophiles to afford hybrid flavonoids.

/pdf/a-bio-inspired-synthesis-of-hybrid-flavonoids-from-2-4hcbhb2wie.pdf

A bio-inspired synthesis of hybrid flavonoids from 2-hydroxychalcone driven by visible light

Halocyclization of olefinic substrate enables establishment of cyclic skeletons via intramolecular halonium-induced nucleophilic addition, which have been well utilized as a practical strategy for constructing cyclic skeleton in natural product synthesis. Recently, the renaissance and rapid evolution of organocatalysis accelerate the development of catalytic asymmetric halocyclization. In this context, natural product synthesis powered by catalytic asymmetric halocyclization has also received considerable progresses in recent years. In seom cases, these newly developed protocols enable more concise synthetic routes for accessing enantioenriched natural products. To this end, this review summarized the applications of catalytic asymmetric halocyclization in natural product synthesis.

The Applications of Catalytic Asymmetric Halocyclization in Natural Product Synthesis

Au(I)-Catalyzed Domino Cyclization of 1,6-Diynes Incorporated with Indole.

Herein, we disclosed a catalytic asymmetric dearomatization (CADA) of tryptamine via tandem [4 + 2] cycloaddition/cyclization with o-azaxylylene in situ generated from functionalized 3-bromooxindole promoted by chiral N,N′-dioxide/Ni(BF4)2. A variety of dimeric tryptamine derivatives with meso-contiguous quaternary carbon centers were obtained with good to excellent enantioselectivities and diastereoselectivities from Na-unprotected or protected tryptamines. A formal asymmetric synthesis of hodgkinsine B was also executed to showcase its synthetic potential.

The catalytic asymmetric dearomatization of tryptamine for accessing meso-contiguous quaternary carbon centers of oligomeric cyclotryptamine alkaloids: a formal synthesis of hodgkinsine B

Guzhou Chen

Papers

A bio-inspired synthesis of hybrid flavonoids from 2-hydroxychalcone driven by visible light

The Applications of Catalytic Asymmetric Halocyclization in Natural Product Synthesis

Au(I)-Catalyzed Domino Cyclization of 1,6-Diynes Incorporated with Indole.

The catalytic asymmetric dearomatization of tryptamine for accessing meso-contiguous quaternary carbon centers of oligomeric cyclotryptamine alkaloids: a formal synthesis of hodgkinsine B

Concise syntheses of (+)-austrodoral and (+)-austrodoric acid Based on H2O2 mediated oxidative ring contraction