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.
| Original language | English |
|---|---|
| Article number | e202400477 |
| Pages (from-to) | 1-5 |
| Number of pages | 5 |
| Journal | Chemistry - A European Journal |
| Volume | 30 |
| Issue number | 29 |
| Early online date | 18 May 2024 |
| DOIs | |
| Publication status | Published - 23 May 2024 |
Bibliographical note
Publisher Copyright:© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.
Funding
This publication is part of the project Unified Access to Kopsia and Aspidosperma Alkaloids by a Stereoselective Cascade Cyclization (project number 713.018.001) of the research programme CW ECHO which is financed by the Dutch Research Council (NWO). We thank H. Daniel Preschel (VUA) for HRMS measurements.
| Funders | Funder number |
|---|---|
| Nederlandse Organisatie voor Wetenschappelijk Onderzoek |
Keywords
- Alkaloids
- DFT calculations
- isocyanides
- molecular diversity
- multicomponent reactions