Synthesis of Biologically Active Carbazole Alkaloids Using Selective Transition-metal-catalyzed Coupling Reactions

Abstract

Highly convergent syntheses of substituted carbazoles are most conveniently achieved using organometallic chemistry. Construction of the carbazole framework via the iron-mediated route proceeds by a sequence of C-C and C-N bond formation. In the highly efficient palladium-catalyzed route the C-N bond is formed first followed by generation of the C-C bond. This article highlights some recent developments and applications to the total synthesis of biologically active carbazole alkaloids. Ç IntroductionThe chemistry and biology of carbazole alkaloids has attracted an increasing interest over the last 50 years. Important milestones for the tremendous development of this class of natural products were the isolation of ellipticine (1) Since then a broad range of structurally interesting carbazole alkaloids with useful biological activities has been isolated from diverse natural sources.3,4 The pharmacological potential of these natural products initiated the development of novel synthetic methods for efficient routes to carbazoles. 4 We have established an iron-mediated and a palladium-catalyzed route, which are based on transition metal-induced coupling reactions of arylamines. 5 The present article briefly summarizes these achievements and shows recent applications to total synthesis.

Transition‐Metal‐Catalyzed Direct Arylation of (Hetero)Arenes by CH Bond Cleavage

“…In an early example, enaminone 67 was cyclized with catalytic amounts of Pd(OAc) 2 and Cu(OAc) 2 under aerobic reaction conditions (Scheme 24). [47,48] Major contributions by the research groups of Akermark and Knoelker [46,49] set the stage for modular access to various naturally occurring carbazole and indole derivatives with valuable biological activities (Scheme 25). [50][51][52] More recently, Ohno and co-workers applied this strategy to a flexible synthesis of diversely substituted carbazoles.…”

Übergangsmetallkatalysierte direkte Arylierungen von (Hetero)Arenen durch C‐H‐Bindungsbruch

“…In einem frühen Beispiel konnte so Enaminon 67 mit katalytischen Mengen Pd(OAc) 2 (OAc) 2 unter aeroben Bedingungen cyclisiert werden (Schema 24). [47,48] Wichtige Beiträge der Arbeitsgruppen von Akermark und Knoelker [46,49] schufen die Grundlage für einen modularen Zugang zu einer Vielzahl von natürlichen, biologisch aktiven Carbazol-und Indolderivaten (Schema 25). [50][51][52] Erst kürlich nutzten Ohno et al diese Strategie bei einer sehr flexiblen Synthese von unterschiedlich substituierten Carbazolen.…”

Total Synthesis of Carbazomycins A and B

“…[1][2][3][4][5][6] Among them, carbazomycins have a simple structure, but attractive biological activities. Especially, carbazomycins A and B, which were isolated from the extract of cultured mycelia of Streptoverticillium ehimensis strain H1051-MY10 [7][8][9] (Chart 1), show inhibitory activity against 5-lipoxygenase, and have weak antibacterial and antiyeast activities.…”