Volume 2018, Issue 47 p. 6714-6719
Communication

Glutarimide Alkaloids Through Multicomponent Reaction Chemistry

Markella Konstantinidou

Markella Konstantinidou

Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands

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Katarzyna Kurpiewska

Katarzyna Kurpiewska

Faculty of Chemistry, Jagiellonian University, 3 Ingardena Street, 30-060 Krakow, Poland

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Justyna Kalinowska-Tłuscik

Justyna Kalinowska-Tłuscik

Faculty of Chemistry, Jagiellonian University, 3 Ingardena Street, 30-060 Krakow, Poland

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Alexander Dömling

Corresponding Author

Alexander Dömling

Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands

Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands

E-mail: [email protected]

http://www.drugdesign.nl/

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Dedicated to Nobel laureate Robert Huber on the occasion of his 80th birthday
First published: 24 September 2018
Citations: 15

Graphical Abstract

A mild four-step synthetic methodology for glutarimide alkaloids was established, based on the Ugi 4-component reaction. Four natural products were synthesized, followed by the synthesis of a small library of derivatives. The stereochemistry, scope, and limitations of the methodology were investigated.

Abstract

A concise four step synthetic route for glutarimide alkaloids of high biological interest is presented. The scaffold is accessed via an Ugi four component reaction, hereby introducing two points of variation. This is followed by a hydrolysis, a cyclization under mild conditions, and an amine deprotection. The diastereomers of the cyclized intermediate can be easily separated, thus leading to optically pure alkaloids. By this route, four natural products and ten derivatives were synthesized. The scope and limitations of the synthetic methodology were investigated.