Totalsynthese komplexer Cyclotryptaminalkaloide: stereokontrollierter Aufbau quartärer Kohlenstoffstereozentren

Abstract

Die Cyclotryptamine sind eine Familie von Alkaloiden mit sehr unterschiedlichen biologischen Aktivitäten. Die komplexeren Mitglieder dieser Naturstoffklasse sind durch benachbarte quartäre Kohlenstoffzentren charakterisiert und wegen der schwierig aufzubauenden, oligomeren Polyindolinstruktur schwer zugänglich. In den letzten Jahren konnten wir eine Reihe von Methoden entwickeln, die einen einfachen Zugang zu Polyindolinen ermöglichen; einige dieser Methoden nutzen Palladiumkatalysatoren zum Aufbau von Kohlenstoff‐Kohlenstoff‐Bindungen mit beeindruckenden Regio‐ und Stereoselektivitäten. In diesem Aufsatz schildern wir die Entwicklung eines Repertoires an Synthesemethoden und deren Anwendung in den Totalsynthesen einiger strukturell komplexer Cyclotryptamine. Insbesondere zeigen wir auf, wie es gelingen kann, mithilfe asymmetrischer Katalysen komplexe, hochfunktionalisierte Moleküle aufzubauen.

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

“…The literature contains a few reviews, although these appear to cover only specific aspects of these compounds. These include works by Schmidt and Movassaghi, [97] on biosynthetic hypotheses; Steven and Overman, [98] on syntheses of poly-HPI compounds; and Crich and Banerjee, [99] on the stereochemistry of HPI containing-compounds, as well as classical publications on the Calabar bean alkaloids, [100,101] phenserine, [102] chimonanthine and related natural products, [103,104] chaetocin and related natural products, [105] and the chemistry of cyclic tautomers of tryptamines and Trp. [106,107] This article provides an exhaustive overview of the structure, synthesis and bioactivity of HPI and HPIC containing natural products from all of the aforementioned structural classes, emphasizing the synthetic routes to polycyclic compounds of this type published until December 2009.…”

“…Alkaloids containing a poly-HPI linked at the quaternary carbons, such as quadrigemine C, have been omitted here because they have already been covered in an excellent report by Steven and Overman. [98] Syntheses of Natural Products Containing HPI or HPIC …”

CH Functionalization/Asymmetric Michael Addition Cascade Enabled by Relay Catalysis: Metal Carbenoid Used for CC Bond Formation

“…[22][23][24]26] In the progress towards enantioselective construction of the core dimeric hexahydropyrroloindoles, we reported the first catalytic asymmetric total synthesis of (+)-folicanthine. [22a] Later, Kanai and Matsunaga developed a chiral manganese-complex-catalyzed double Michael addition of bis(oxindole) for the synthesis of (+)-folicanthine.…”

Oxaziridine‐Mediated Oxyamination of Indoles: An Approach to 3‐Aminoindoles and Enantiomerically Enriched 3‐Aminopyrroloindolines

“…[1] Nature presumably produces these architecturally fascinating compounds through electrophilic cyclization cascades involving appropriately functionalized tryptamine and tryptophan precursors. [1] Nature presumably produces these architecturally fascinating compounds through electrophilic cyclization cascades involving appropriately functionalized tryptamine and tryptophan precursors.…”