Preparation of functional benzofurans and indoles via chemoselective intramolecular Wittig reactions

Lee, Yu Ting; Jang, Yeong Jiunn; Syu, Siang En; Chou, Shu Chi; Lee, Chia Jui; Lin, Wenwei

doi:10.1039/c2cc33972b

Cited by 38 publications

(10 citation statements)

References 23 publications

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“…Licochalcone A was purchased from Sigma-Aldrich (St. Louis, MO, USA). In-house LM compounds LM-004, LM-006, LM-016, LM-026, and LM-031 were synthesized and characterized by NMR spectrum as described previously [43][44][45]. All compounds were soluble in a cell culture medium up to 100 μM.…”

Section: Methodsmentioning

confidence: 99%

New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models

Chen

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Spinocerebellar ataxia type 17 (SCA17) is caused by a CAG/CAA expansion mutation encoding an expanded polyglutamine (polyQ) tract in TATA-box binding protein (TBP), a general transcription initiation factor. Suppression of cAMP-responsive element binding protein- (CREB-) dependent transcription, impaired nuclear factor erythroid 2-related factor 2 (NRF2) signaling, and interaction of AMP-activated protein kinase (AMPK) with increased oxidative stress have been implicated to be involved in pathogenic mechanisms of polyQ-mediated diseases. In this study, we demonstrated decreased pCREB and NRF2 and activated AMPK contributing to neurotoxicity in SCA17 SH-SY5Y cells. We also showed that licochalcone A and the related in-house derivative compound 3-benzoyl-5-hydroxy-2H-chromen-2-one (LM-031) exhibited antiaggregation, antioxidative, antiapoptosis, and neuroprotective effects in TBP/Q79-GFP-expressing cell models. LM-031 and licochalcone A exerted neuroprotective effects by upregulating pCREB and its downstream genes, BCL2 and GADD45B, and enhancing NRF2. Furthermore, LM-031, but not licochalcone A, reduced activated AMPKα. Knockdown of CREB and NRF2 and treatment of AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside), an AMPK activator, attenuated the aggregation-inhibiting and neurite outgrowth promoting effects of LM-031 on TBP/Q79 SH-SY5Y cells. The study results suggest the LM-031 as potential therapeutics for SCA17 and probable other polyQ diseases.

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Section: Methodsmentioning

confidence: 99%

New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models

Chen

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Lico A, coumarin, and curcumin were purchased from Sigma‐Aldrich, St. Louis, MO, USA. The Lico A derivatives LM‐004 and LM‐006 and the coumarin derivative LM‐016 were synthesized according to previous reports . LM‐026 was synthesized using the procedure reported by Mazimba et al with some modifications, and LM‐031 was synthesized using the procedures reported by Dube et al and Tietze et al with some modifications.…”

Section: Methodsmentioning

confidence: 99%

Novel synthetic chalcone‐coumarin hybrid for Aβ aggregation reduction, antioxidation, and neuroprotection

et al. 2018

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Background Aggregation of misfolded amyloid β (Aβ) in senile plaques causes oxidative stress and neuronal death in Alzheimer's disease (AD). Compounds possessing antiaggregation and antioxidant properties are promising candidate compounds for AD treatment. Methods We examined the potential of synthetic derivatives of licochalcone A and coumarin for inhibiting Aβ aggregation, scavenging reactive oxygen species (ROS), and providing neuroprotection by using biochemical assays and Tet‐On Aβ‐GFP 293/SH‐SY5Y cell models for AD. Results Among test compounds, LM‐031, a novel chalcone‐coumarin hybrid, inhibited Aβ aggregation and scavenged free oxygen radicals. LM‐031 markedly reduced Aβ misfolding and ROS as well as promoted neurite outgrowth and inhibited acetylcholinesterase in Tet‐On Aβ‐GFP 293/SH‐SY5Y cells. Mechanistic studies showed upregulation of the HSPB1 chaperone, NRF2/NQO1/GCLC pathway, and CREB/BDNF/BCL2 pathway. Decreased neurite outgrowth upon the induction of Aβ‐GFP was rescued by LM‐031, which was counteracted by knockdown of HSPB1, NRF2, or CREB. Conclusion Taken together, these findings demonstrate that LM‐031 exhibited antiaggregation, antioxidant, and neuroprotective effects against Aβ toxicity by enhancing HSPB1 and the NRF2‐related antioxidant pathway as well as by activating the CREB‐dependent survival and antiapoptosis pathway. These results imply that LM‐031 may be a new therapeutic compound for AD.

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“…Our primary intention was to generate the bisacylated phosphonium salt 9 from 5 and study the chemoselectivity of intramolecular Wittig reaction, in the presence of two equivalent acyl groups (Scheme ). Accordingly, 5 b was treated with TFAA ( 8 a ) and Et 3 N in THF at 30 °C.…”

Section: Methodsmentioning

confidence: 99%

Diversity‐Oriented Synthesis of Furo[3,2‐c]coumarins and Benzofuranyl Chromenones through Chemoselective Acylation/Wittig Reaction

et al. 2018

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A highly efficient and chemoselective one‐pot protocol for the diversity‐oriented synthesis of two types of coumarin‐based formal cross‐coupling adducts, furo[3,2‐c]coumarins and 3‐benzofuranyl chromenones, is described. Key attributes of the methodology are an initial chemoselective acylation of functionalized phosphorus zwitterions and a subsequent chemoselective intramolecular Wittig reaction that preferentially resulted in one of the two coumarin derivatives in high yield, depending on relative reactivities and the addition sequence of the acylating agents.

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Preparation of functional benzofurans and indoles via chemoselective intramolecular Wittig reactions

Cited by 38 publications

References 23 publications

New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models

New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models

Novel synthetic chalcone‐coumarin hybrid for Aβ aggregation reduction, antioxidation, and neuroprotection

Diversity‐Oriented Synthesis of Furo[3,2‐c]coumarins and Benzofuranyl Chromenones through Chemoselective Acylation/Wittig Reaction

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