2-tert-Butyl-5,6,7,8,9,10-hexahydrocyclohepta[b]indole

Falke, Hannes; Bumiller, Katharina; Harbig, Sabrina; Masch, Andreas; Wobbe, Janina; Kunick, Conrad

doi:10.3390/m737

Cited by 5 publications

(4 citation statements)

References 11 publications

(17 reference statements)

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“…This section exclusively deals with the construction of this structure motif. Formation of benzocyclohepta[ b ]indoles, ,− and carbocycle-fused indoles, also suitable for the generation of cyclohepta[ b ]indoles, are not covered here. − …”

Section: Methodologies For Construction Of Cyclohepta[b]indolesmentioning

confidence: 99%

Cyclohepta[b]indoles: A Privileged Structure Motif in Natural Products and Drug Design

2016

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Seven-membered rings fused with an indole are termed cyclohepta[b]indoles. Compounds exhibiting this structure motif display a broad spectrum of biological activities, ranging from inhibition of adipocyte fatty-acid-binding protein (A-FABP), deacetylation of histones, inhibition of leukotriene production p53, antituberculosis activities, and anti-HIV activities. These biological profiles are found in natural products containing the cyclohepta[b]indole motif, as well as in pharmaceuticals that contain this structure motif. Therefore, the biology of molecules derived from the skeleton of cyclohepta[b]indoles, as well as cyclopenta- and cyclohexa[b]indoles, has attracted considerable interest from the pharmaceutical industry as potential therapeutics in recent years. This is reflected by more than two dozen patents that have been issued in the past decade, solely based on the cyclohepta[b]indole structure motif. The efficient preparation of highly functionalized and unsymmetrically substituted cyclohepta[b]indoles has therefore become of central interest for synthetic organic chemists. Historically, this structure motif most often has been prepared by means of a Fischer indole synthesis. Although very robust and useful, this reaction poses certain limitations. Especially unsymmetrically functionalized cyclohepta[b]indoles are not suitable for a Fischer indole type synthesis, since product mixtures are inevitable. Therefore, novel methodologies to overcome these synthetic obstacles have been developed in recent years. This Account introduces all natural products and pharmaceutical compounds exhibiting the cyclohepta[b]indole motif. The structural variability within cyclohepta[b]indole alkaloids in combination with the broad range of organisms where these alkaloids have been isolated from, strongly suggests that the cyclohepta[b]indole is somehow a "privileged" structure motif. The organisms producing these compounds range from evergreen trees (actinophyllic acid) to cyanobacteria (ambiguinines). The synthetic methodologies to construct these molecular scaffolds (natural and unnatural in origin) are in turn highlighted and discussed with regard to their potential to access highly functionalized and unsymmetrical cyclohepta[b]indoles, for which they specifically have been designed. The methods are classified with respect to reaction type and whether or not they are enantioselective. Finally, the syntheses of cyclohepta[b]indole natural products are presented, thereby in each case, focusing on the construction of this structure motif in the course of the respective total synthesis. As a conclusion, we end by contrasting the methodological progress in the field with the actual successful application of the newly developed methods to the synthesis of complex structures to pinpoint the urgent requirement for further synthetic development for efficient synthetic design of this "privileged" structure motif.

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Section: Methodologies For Construction Of Cyclohepta[b]indolesmentioning

confidence: 99%

Cyclohepta[b]indoles: A Privileged Structure Motif in Natural Products and Drug Design

2016

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“…Recently, highly innovative metal-catalyzed paullone syntheses have been reported [12,13,16,17]. However, for the sake of simplicity we employed a standard acid-induced Fischer indolization procedure [18] for the preparation of 4, starting from 8-chloro-3,4-dihydro-1H-1-benzazepine-2,5-dione (2) [19] and commercially available 4-bromophenylhydrazine hydrochloride (3) (Scheme 1). …”

Section: M856 (Page 2)mentioning

confidence: 99%

3-Chlorokenpaullone

Orban

Unger

Yildiz

et al. 2015

Molbank

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Abstract:3-Chlorokenpaullone (9-bromo-3-chloro-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one) is a novel derivative of the protein kinase inhibitor kenpaullone. The title compound was synthesized by a Fischer indole reaction from 8-chloro-3,4-dihydro-1H-1-benzazepin-2,5-dione and 4-bromophenylhydrazine. It was characterized for structural identity by elemental analysis and spectroscopic methods (IR, NMR, EI-MS) and checked for purity by HPLC.

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“…In recent years, inhibitors of tumor-related protein kinases were established as major therapeutic options for the treatment of various human cancers [1,2]. In the context of our studies directed to identify new protein kinase inhibitors based on the indole structure [3][4][5][6][7], we were interested in the synthesis of the title compound 7-bromo-1-methyl-2-phenyl-1H-indole 3-carbonitrile (3). (2).…”

Section: Introductionmentioning

confidence: 99%