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Updated: Jun 30, 2025

Optimization of the Ugi Reaction Using Parallel Synthesis and Automated Liquid Handling
Published on: November 11, 2008
Modular Divergent Synthesis of Indole Alkaloid Derivatives by an Atypical Ugi Multicomponent Reaction
Brendan Horst1, Niels van Duijnen1, Elwin Janssen1
1Department of Chemistry and Pharmaceutical Sciences, Amsterdam Institute for Molecular & Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081, HZ Amsterdam, The Netherlands.
Abstract:
We present an Ugi multicomponent approach to explore the chemical space around Aspidosperma-type monoterpene indole alkaloids. By variation of the isocyanide and carboxylic acid inputs we demonstrate the rapid generation of molecular diversity and the possibility to introduce handles for further modification. The key Ugi three-component reaction showed full diastereoselectivity towards the cis-fused ring system, which can be rationalized by DFT calculations that moreover indicate that the reaction proceeds via a Passerini-type hydrogen bonding mechanism. Several post-Ugi modifications were also performed, including Pictet-Spengler cyclization to highly complex nonacyclic natural product hybrid scaffolds.
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