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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Vydané v:	Angewandte Chemie Ročník 127; číslo 47; s. 14339 - 14342
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English German
Vydavateľské údaje:	Weinheim WILEY‐VCH Verlag 16.11.2015 Wiley Subscription Services, Inc
Predmet:	Asymmetric synthesis Asymmetrische Synthesen Asymmetry Biologisch aktive Verbindungen Capsaicin receptors Cascade chemical reactions Chemistry Cholinesterase Cholinesterase inhibitors Constraints Derivatives Functional groups Imines Indoles Inhibitors Ion channels Reaction mechanisms Reaktionskaskaden Serotonin Stoichiometry Synthesemethoden Synthesis (chemistry) Tryptamine Tryptamines
ISSN:	0044-8249, 1521-3757
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Popis
Shrnutí:	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. Am Scheideweg: Unterbrochene Fischer‐Indolsynthesen mit Arylhydrazinen und chiralen bicyclischen Iminen ergeben abhängig von den Reaktionsbedingungen selektiv entweder tetracyclische Pyrroloindoline oder tricyclische Tryptamin‐Analoga. Die optisch hoch reinen Produkte lassen sich leicht in medizinisch bedeutende Verbindungen umsetzen.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0044-8249 1521-3757
DOI:	10.1002/ange.201507041