Asymmetric Synthesis of Tetracyclic Pyrroloindolines and Constrained Tryptamines by a Switchable Cascade Reaction

The interrupted Fischer indole synthesis of arylhydrazines and biocatalytically generated chiral bicyclic imines selectively affords either tetracyclic pyrroloindolines or tricyclic tryptamine analogues depending on the reaction conditions. We demonstrate that the reaction is compatible with a varie...

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Veröffentlicht in:	Angewandte Chemie International Edition Jg. 54; H. 47; S. 14133 - 14136
Hauptverfasser:	de Graaff, Corien, Bensch, Lisa, Boersma, Sjoerd J., Cioc, Răzvan C., van Lint, Matthijs J., Janssen, Elwin, Turner, Nicholas J., Orru, Romano V. A., Ruijter, Eelco
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Weinheim WILEY-VCH Verlag 16.11.2015 WILEY‐VCH Verlag Wiley Wiley Subscription Services, Inc
Ausgabe:	International ed. in English
Schlagworte:	asymmetric synthesis bioactive compounds cascade reactions Chemistry Chemistry, Multidisciplinary Cholinesterase Cholinesterase inhibitors Indoles - chemical synthesis Indoles - chemistry Molecular Structure Physical Sciences Pyrroles - chemical synthesis Pyrroles - chemistry Science & Technology synthetic methods tryptamines Tryptamines - chemical synthesis Tryptamines - chemistry cascade reactions asymmetric synthesis ENANTIOSELECTIVE SYNTHESIS tryptamines bioactive compounds DERIVATIVES synthetic methods ARYLBORONIC ACIDS DESYMMETRIZATION
ISSN:	1433-7851, 1521-3773, 1521-3773
Online-Zugang:	Volltext
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Zusammenfassung:	The interrupted Fischer indole synthesis of arylhydrazines and biocatalytically generated chiral bicyclic imines selectively affords either tetracyclic pyrroloindolines or tricyclic tryptamine analogues depending on the reaction conditions. We demonstrate that the reaction is compatible with a variety of functional groups. The products are obtained in high optical purity and in reasonable to good yield. We present a plausible reaction mechanism to explain the observed reaction outcome depending on the stoichiometry of the acid mediator. To demonstrate the synthetic utility of our method, pharmaceutically relevant examples of both product classes were synthesized in highly efficient reaction sequences, including a phenserine analogue as a potential cholinesterase inhibitor and constrained tryptamine derivatives as selective inhibitors of the 5‐HT6 serotonin receptor and the TRPV1 ion channel. One way or the other: The interrupted Fischer indole synthesis of arylhydrazines and chiral bicyclic imines selectively affords either tetracyclic pyrroloindolines or tricyclic tryptamine analogues depending on the reaction conditions. The products were obtained in high optical purity and readily elaborated to medicinally important compounds.
Bibliographie:	ark:/67375/WNG-3HHPH47K-8 istex:A94C69AD4800B766D63F3E4C83A953FB5F20C5D1 Royal Society Netherlands Organization for Scientific Research (NWO) ArticleID:ANIE201507041 NSF - No. 1337296 National Science Foundation ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1433-7851 1521-3773 1521-3773
DOI:	10.1002/anie.201507041