Telescoped Synthesis of 2-Acyl-1-aryl-1,2-dihydroisoquinolines and Their Inhibition of the Transcription Factor NF-κB

Abstract

A sequential single-flask multicomponent reactions is highly effective for the synthesis of 1,2-dihydroisoquinolines through amidealkylation from intermediate N-acylisoquinolinium salts under mild conditions. N-Acylisoquinolinium ions and trichloromethyl-1-(1H-indol-3-yl)isoquinoline-2(1H)-carboxylate have demonstrated their reactivity toward aromatic and aliphatic π-nucleophiles. One of the 1,2-dihydroisoquinoline derivatives was found to be a potent inhibitor for transcription factor NF-κB by blocking IκBα degradation, p65 nuclear translocation, and NF-κB DNA binding in TNF-α-induced NIH 3T3 cells.

Expedient Synthesis of Dihydroisoquinolines by Cascade Annulation of Nitrovinylbenzoquinone

“…1,2‐Dihydroisoquinolines are important structural units of many natural alkaloids and pharmaceuticals that exhibited many biological activities such as inhibition of HIV‐1 integrase, inhibition of the transcription factor NF‐κB, antitumor activity, neurotropic activity and antidepressant activity . Therefore, synthesis of 1,2‐dihydroisoquinolines has attracted much attention .…”

Synthesis of Indole-Dihydroisoquinoline Sulfonyl Ureas via Three-Component Reactions

“…Recently, Chung and co-workers described libraries of indole-dihydroisoquinoline amides, ureas and sulfonamides (although not sulfonyl ureas). 8 However, the sulfonamides were not well explored (only 4 examples) and only unsubstituted isoquinoline was used. Also, their procedure…”

“…Other functionalised isoquinolines were accessed by functional group interconversions. For example, coppercatalysed coupling of 6-bromoisoquinoline (8) to sodium methanesulfinate gave sulfone 14. Suzuki coupling of 8 to a vinyl trifluoroborate salt followed by hydrogenation of the resulting alkene gave 22 (Scheme 5).…”

TMSCl-Catalyzed Tandem Reaction of Dihydroisobenzofuran Acetals with Indoles

“…For example, the α-phenylisoquinoline solifenacin is an FDA-approved drug for urge incontinence [6]. α-Indolisoquinoline-like IBR2 has a significant inhibitory effect on triple-negative human breast cancer cells [7][8][9][10]. Such compounds are typically prepared by metal catalyzed cross-dehydrogenative coupling.…”