Diverting β-Hydride Elimination of a π-Allyl Pd<sup>II</sup> Carbene Complex for the Assembly of Disubstituted Indolines via a Highly Diastereoselective (4 + 1)-Cycloaddition

Tucker, Zachary D.; Hill, Harrison; Smith, Andrew Lee; Ashfeld, Brandon L.

doi:10.1021/acs.orglett.0c02374

Cited by 22 publications

(12 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It would provide dihydroindole ( 13 ) via sequential, intramolecular C−C and C−N bond formations from π‐allyl Pd complex (Scheme 4). [8] The resulting 2,3‐disubstituted dihydroindoles were obtained in moderate to high yields and with exceptional levels of diastereoselectivity (dr >20:1).…”

Section: Vinyl Benzoxazinones As a “14‐dipole” In [4+1] Annulationsmentioning

confidence: 98%

Recent Advances in Metal‐Catalyzed Decarboxylative Reactions of Vinyl Benzoxazinanones

et al. 2021

View full text Add to dashboard Cite

Vinyl benzoxazinanones as versatile building blocks can undergo transition‐metal‐catalyzed decarboxylation to enable various kinds of interesting transformations by various [4+n], transition‐metal‐catalyzed C−H allylation of arenes and other types of annulations. Herein, we reviewed the latest research progress in the research and application of vinyl benzoxazinones in metal‐catalyzed decarboxylative reactions to illustrate their synthetic value.

show abstract

Section: Vinyl Benzoxazinones As a “14‐dipole” In [4+1] Annulationsmentioning

confidence: 98%

Recent Advances in Metal‐Catalyzed Decarboxylative Reactions of Vinyl Benzoxazinanones

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The vinyl indolines 4 were synthesized employing a recently reported Pd 0 ‐catalyzed (4+1)‐cycloaddition between sulfonyl hydrazones 11 and carbamates 12 (Figure 4c) [62] . The utilization of the well‐established carbamate starting material afforded access to a diverse array of electron withdrawing and electron donating arene substitution.…”

Section: Figurementioning

confidence: 99%

Rational Design and Identification of Harmine‐Inspired, N‐Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System**

et al. 2022

Self Cite

View full text Add to dashboard Cite

Deregulation of dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A) plays a significant role in developmental brain defects, early‐onset neurodegeneration, neuronal cell loss, dementia, and several types of cancer. Herein, we report the discovery of three new classes of N‐heterocyclic DYRK1A inhibitors based on the potent, yet toxic kinase inhibitors, harmine and harmol. An initial in vitro evaluation of the small molecule library assembled revealed that the core heterocyclic motifs benzofuranones, oxindoles, and pyrrolones, showed statistically significant DYRK1A inhibition. Further, the utilization of a low cost, high‐throughput functional genomic in vivo model system to identify small molecule inhibitors that normalize DYRK1A overexpression phenotypes is described. This in vivo assay substantiated the in vitro results, and the resulting correspondence validates generated classes as architectural motifs that serve as potential DYRK1A inhibitors. Further expansion and analysis of these core compound structures will allow discovery of safe, more effective chemical inhibitors of DYRK1A to ameliorate phenotypes caused by DYRK1A overexpression.

show abstract

“…Vinyl indoline materials were generated utilizing a previously reported method with spectra matching reported data. 12…”

Section: Iv: Experimental Details For the Synthesis Of Scaffoldsmentioning

confidence: 99%

Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic in vivo Drosophila Model System

Ashfeld¹,

Huizar²,

Hill³

et al. 2021

Preprint

View full text Add to dashboard Cite

Deregulation of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) plays a significant role in developmental brain defects, early-onset neurodegeneration, neuronal cell loss, and dementia. Herein, we report the discovery of three new classes of <i>N</i>-heterocyclic DYRK1A inhibitors based on the potent, yet toxic kinase inhibitors, harmine and harmol. An initial in vitro evaluation of the small molecule collection assembled revealed that the core heterocyclic motifs benzofuranones, oxindoles, and pyrrolones, showed statistically significant DYRK1A inhibition. Further, the utilization of a low cost, high-throughput functional genomic in vivo model system to identify small molecule inhibitors that normalize DYRK1A overexpression phenotypes is described. This in vivo assay confirmed the in vitro results, and the resulting correspondence validates generated classes as architectural motifs that serve as potential DYRK1A inhibitors. Further expansion and analysis of these core compound structures will allow discovery of safe, more effective chemical inhibitors of DYRK1A to ameliorate phenotypes caused by DYRK1A overexpression.

show abstract

Diverting β-Hydride Elimination of a π-Allyl Pd^II Carbene Complex for the Assembly of Disubstituted Indolines via a Highly Diastereoselective (4 + 1)-Cycloaddition

Cited by 22 publications

References 55 publications

Recent Advances in Metal‐Catalyzed Decarboxylative Reactions of Vinyl Benzoxazinanones

Recent Advances in Metal‐Catalyzed Decarboxylative Reactions of Vinyl Benzoxazinanones

Rational Design and Identification of Harmine‐Inspired, N‐Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System**

Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic in vivo Drosophila Model System

Contact Info

Product

Resources

About

Diverting β-Hydride Elimination of a π-Allyl PdII Carbene Complex for the Assembly of Disubstituted Indolines via a Highly Diastereoselective (4 + 1)-Cycloaddition

Cited by 22 publications

References 55 publications

Recent Advances in Metal‐Catalyzed Decarboxylative Reactions of Vinyl Benzoxazinanones

Recent Advances in Metal‐Catalyzed Decarboxylative Reactions of Vinyl Benzoxazinanones

Rational Design and Identification of Harmine‐Inspired, N‐Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System**

Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic in vivo Drosophila Model System

Contact Info

Product

Resources

About

Diverting β-Hydride Elimination of a π-Allyl Pd^II Carbene Complex for the Assembly of Disubstituted Indolines via a Highly Diastereoselective (4 + 1)-Cycloaddition