A new approach to 1-substituted β-carbolines and isoquinolines utilizing tributyl[(Z)-2-ethoxyvinyl]stannane as a C-3,C-4 building block

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

“…In continuation of our recent work on the chemistry and pharmacology of benzylisoquinolines and related compounds [6][7][8][9][10][11][12][13][14] we investigated truncated analogues of the bisbenzylisoquino-line alkaloid tetrandrine as blockers of the calcium channel twopore channel 2 (TPC2), and identified 1-benzyl-1,2,3,4-tetrahydroisoquinolines bearing phenoxy and benzyloxy substituents (SG-005, SG-094; for structures of bioactive compounds mentioned in this text, see Figure S1 in Supporting Information File 1) on both aromatic rings as potent blockers with promising antitumor activity [15]. In this work we took advantage of the hitherto less explored N-acyl-Pictet-Spengler reaction and related chemistry based on the seminal work of Speckamp [16], where an N-acyl residue at the arylethylamine building block leads to enhanced cyclization rates due to the acid-mediated formation of highly electrophilic N-acyliminium intermediates [17].…”

Design and Synthesis of Fluorescent 1,3-Diaryl-β-carbolines and 1,3-Diaryl-3,4-dihydro-β-carbolines

“…There are limited reports describing the synthesis of β-carbolines with aryl substitution at the C1 and C3 positions. In most cases, the resulting modified β-carbolines were arylated exclusively at either C1 or C3; in only a few cases were 1,3-diphenyl-β-carbolines successfully synthesized (Scheme ). The structure–activity relationship analyses revealed that 1-aryl-substitution on a β-carboline bearing a carbohydrazide moiety at C3 enhanced the antitumor activity .…”

General Method for the Preparation of Indole-2-Weinreb Amides

“…2,3 In the course of our ongoing research on bioactive βcarbolines, 4 2-acylindoles were identified as attractive building blocks for the synthesis of 1-substituted β-carbolines. 5 In general, 2-acylindoles are available from N-protected (carboxylate, arenesulfonyl) 2-lithioindoles and acyl electrophiles, 6 from anilines bearing various ortho-substituents, 7,8 from ortho-bromochalcones and sodium azide, 9 or by Rh-catalyzed reaction of azobenzenes and vinyl ketones. 10 However, most of these approaches require highly substituted, poorly available benzenes as precursors.…”

“…A viable approach to highly substituted 2-acylindoles consists of the reaction of appropriate indole-2-Weinreb amides (Nmethoxy-N-methylamides) with organolithium or Grignard reagents. 5,11 This conversion proceeds via a stable tetrahedral metal-chelated intermediate to form, after aqueous hydrolysis, the ketones. 12 The required Weinreb amides are commonly prepared from N,O-dimethylhydroxylamine and the corresponding indole-2-carboxylates via the acid chloride or by using conventional amide coupling reagents, or from the corresponding esters by reaction with N,O-dimethylhydroxylamine in the presence of Lewis acids.…”