Diastereoselective aldol-type interception of phenolic oxonium ylides for the direct assembly of 2,2-disubstituted dihydrobenzofurans

Hong, Kemiao; Yang, Xiangji; Zhang, Zhijing; Xie, Xiongda; Lv, Xin; Xu, Xinfang; Hu, Wenhao

doi:10.1039/d2ob00723a

Cited by 5 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3g belongs to a newly synthesized compound library that utilizes a novel and environmentally sustainable catalytic method, resulting in remarkable yields. 24 Furthermore, there have been no studies investigating the bioactivities of compounds with this structure in ion channels. Our research is the first to demonstrate that it acts on Nav1.7 and possesses antinociceptive properties.…”

Section: ■ Discussionmentioning

confidence: 99%

Nav1.7 Modulator Bearing a 3-Hydroxyindole Backbone Holds the Potential to Reverse Neuropathic Pain

Wang,

Shu,

Yang

et al. 2024

ACS Chem. Neurosci.

Self Cite

View full text Add to dashboard Cite

Chronic pain is a growing global health problem affecting at least 10% of the world's population. However, current chronic pain treatments are inadequate. Voltage-gated sodium channels (Navs) play a pivotal role in regulating neuronal excitability and pain signal transmission and thus are main targets for nonopioid painkiller development, especially those preferentially expressed in dorsal root ganglial (DRG) neurons, such as Nav1.6, Nav1.7, and Nav1.8. In this study, we screened in virtual hits from dihydrobenzofuran and 3-hydroxyoxindole hybrid molecules against Navs via a veratridine (VTD)-based calcium imaging method. The results showed that one of the molecules, 3g, could inhibit VTD-induced neuronal activity significantly. Voltage clamp recordings demonstrated that 3g inhibited the total Na + currents of DRG neurons in a concentration-dependent manner. Biophysical analysis revealed that 3g slowed the activation, meanwhile enhancing the inactivation of the Navs. Additionally, 3g use-dependently blocked Na + currents. By combining with selective Nav inhibitors and a heterozygous expression system, we demonstrated that 3g preferentially inhibited the TTX-S Na + currents, specifically the Nav1.7 current, other than the TTX-R Na + currents. Molecular docking experiments implicated that 3g binds to a known allosteric site at the voltage-sensing domain IV(VSDIV) of Nav1.7. Finally, intrathecal injection of 3g significantly relieved mechanical pain behavior in the spared nerve injury (SNI) rat model, suggesting that 3g is a promising candidate for treating chronic pain.

show abstract

Section: ■ Discussionmentioning

confidence: 99%

Nav1.7 Modulator Bearing a 3-Hydroxyindole Backbone Holds the Potential to Reverse Neuropathic Pain

Wang,

Shu,

Yang

et al. 2024

ACS Chem. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In 2022, Hu 62 et al presented a strategy for the efficient synthesis of 3-hydroxyoxindole incorporating 2,3-dihydrobenzofuran derivatives 83 via a Rh-catalyzed protocol. In their novel approach, diazo-containing phenolic compounds 80 were reacted with isatin 81 through an aldol type addition reaction to afford desired scaffolds 83 in moderate to excellent yields (58–98%) with exclusive diastereoselectivity (81 : 19–95 : 5 dr).…”

Section: Review Of Literaturementioning

confidence: 99%

Development of novel transition metal-catalyzed synthetic approaches for the synthesis of a dihydrobenzofuran nucleus: a review

Ashraf,

Zahoor,

Ali

et al. 2024

RSC Adv.

View full text Add to dashboard Cite

show abstract

“…Transition metal-catalyzed multicomponent reactions (MCRs) involving electrophilic trapping of ammonium ylide intermediates generated in situ from metal carbenoids and N–H bond donors have emerged as a powerful protocol for construction of functional nitrogen compounds with complex structures (Scheme a). Hu, Gong, and others have done outstanding work in trapping ammonium ylides with various electrophilic substances. − Inspired by this precedent, we proposed capturing an ammonium ylide, formed by intramolecular N–H bond insertion into a metal carbene, with a cationic allyl intermediate through Rh/Pd dual catalysis. If feasible, this reaction would constitute a new method to construct 2,2-disubstituted tetrahydroquinoline derivatives.…”

mentioning

confidence: 99%

Rh(II)/Pd(0) Dual Catalysis: Interception of Ammonium Ylide with Allyl Palladium to Construct 2,2-Disubstituted Tetrahydroquinoline Derivatives

Zhang

Liu

et al. 2023

J. Org. Chem.

View full text Add to dashboard Cite

New synthetic methods to construct 2,2-disubstituted tetrahydroquinoline derivatives are of significant value in pharmaceutical chemistry. Herein, a Rh(II)/Pd(0) dual-catalyzed diazo α-aminoallylation reaction has been developed between allylpalladium(II) and ammonium ylides derived from the Rh2(OAc)4-mediated intramolecular N–H bond insertion reaction of diazo compounds, affording various 2,2-disubstituted tetrahydroquinoline derivatives in good yields up to 93% with high chemoselectivities under mild reaction conditions. A substrate scope investigation reveals broad ester substituent tolerance, and control experiments provide the basis for a proposed reaction mechanism.

show abstract

Diastereoselective aldol-type interception of phenolic oxonium ylides for the direct assembly of 2,2-disubstituted dihydrobenzofurans

Abstract: A Rh2(OAc)4 catalyzed intermolecular Aldol-type interception of phenolic oxonium ylides with isatins has been developed that provides an effective access to the 2,2-disubstituted dihydrobenzofuran derivatives containing 3-hydroxyoxindole in high yields...

Cited by 5 publications

References 48 publications

Nav1.7 Modulator Bearing a 3-Hydroxyindole Backbone Holds the Potential to Reverse Neuropathic Pain

Nav1.7 Modulator Bearing a 3-Hydroxyindole Backbone Holds the Potential to Reverse Neuropathic Pain

Development of novel transition metal-catalyzed synthetic approaches for the synthesis of a dihydrobenzofuran nucleus: a review

Rh(II)/Pd(0) Dual Catalysis: Interception of Ammonium Ylide with Allyl Palladium to Construct 2,2-Disubstituted Tetrahydroquinoline Derivatives

Contact Info

Product

Resources

About