Total Synthesis of (±)-Brazilin Using [4 + 1] Palladium-Catalyzed Carbenylative Annulation

Arredondo, Vanessa; Roa, Daniel E.; Gutman, Eugene S.; Huynh, Nancy O.; Vranken, David L. Van

doi:10.1021/acs.joc.9b02343

Cited by 17 publications

(10 citation statements)

References 59 publications

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“…However, the animal models for examine the anti-cancer effects of brazilin were poor therefore these results suggest that required novel candidate for screening of drugs with analogues. Moreover, brazilin has not been used for the clinical treatment of disease, then more basic results and evidences of this natural/synthetic molecules (Jung and Kim, 2015;Arredondo et al, 2019) and analogues are urgently needed.…”

Section: Discussionmentioning

confidence: 99%

Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells

et al. 2022

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The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells.

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Section: Discussionmentioning

confidence: 99%

Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells

et al. 2022

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“…Migratory insertion is another typical insertion reaction of carbenoids.A long this line,V an Vrankensg roup disclosed at otal synthesis of (AE)-brazilin, taking advantage of aC À C bond formation cascade (Scheme 6d). [42] Under palladium catalysis,t he metallocarbene coupled firstly with the aryl iodide (E + )a nd then the malonate anion (Nu À ), which cyclized the starting materials (6.9 and 6.10)e fficiently and manufactured the indane ring of (AE)-brazilin (6.11).…”

Section: Tosylhydrazones For Migratory Insertionmentioning

confidence: 99%

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

Huang

2022

Angewandte Chemie

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The simple and efficient conversion of carbonyl compounds into functionalized alkanes via deoxygenation is highly enabling in chemical synthesis. This Review covers the recent methodology development in carbonyl and carboxyl deoxygenative functionalizations, highlighting some representative and significant contributions in this field. These advances are categorized based on the reactivity patterns of some oxygenated feedstock compounds, including aldehydes, ketones and carboxylic acids. Four types of reactive intermediates arising from aldehydes and ketones during the deoxygenation, namely, bis‐electrophiles, carbenoids, bis‐nucleophiles and alkyl radical equivalents, are presented, while the carboxylic acids mainly behave as tris‐electrophiles when deoxygenated. In each subcategory, selected examples are organized according to the type of bond formation and discussed from a generalized mechanistic perspective.

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“…In their study on total synthesis of (±)‐brazilin ( 182 ), Vranken and co‐workers found that m ‐CPBA epoxidation of olefin 178 generated epoxide 179 as an inseparable 6.5 : 1 mixture of diastereomers (Scheme 42). [56] Chemoselective debenzylation of 179 with Pd(OH) 2 and H 2 was accompanied by spontaneous 5‐ exo EPC to yield the indano[2,1‐ b ]benzofuran 180 instead of their desired indano[2,1‐ c ]chroman ring system 181 of brazilin.…”

Section: Construction Of Benzo‐fused Heterocycles By Epoxide–o‐nucleo...mentioning

confidence: 99%

Construction of Benzo‐Fused Heterocycles by Epoxide–Heteronucleophile Cyclization: Applications in the Synthesis of Natural Products and Designed Molecules

Das

2022

Eur J Org Chem

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Construction of benzo‐fused heterocycles, specifically which have one or more sp3 stereogenic carbon atoms on the heterocyclic ring, by intramolecular ring‐opening cyclization of epoxides with O‐ and N‐nucleophiles is a powerful synthetic tool in organic synthesis. In this Review, we analyze the efficiency of such a heterocyclization approach in natural product synthesis and synthetic methodologies published since the year 2000. In addition to briefly discussing the synthetic methods of accessing the requisite epoxide substrates, important aspects of the subsequent cyclization reaction, such as reaction conditions, endo‐ versus exo‐regioselectivity, protecting or functional group compatibility, and enantio‐ and distereoselectivity are surveyed. Although the literature of organic chemistry in the last four decades has witnessed a large number of reviews/book chapters on the epoxide ring‐opening chemistry, the title topic has never been reviewed. Herein, we have systematized it as a dedicated review for the first time.

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Total Synthesis of (±)-Brazilin Using [4 + 1] Palladium-Catalyzed Carbenylative Annulation

Cited by 17 publications

References 59 publications

Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells

Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

Construction of Benzo‐Fused Heterocycles by Epoxide–Heteronucleophile Cyclization: Applications in the Synthesis of Natural Products and Designed Molecules

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