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Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids
- Source :
- Angewandte Chemie (International Ed. in English)
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- We describe the synthesis and biological evaluation of a new natural product‐inspired compound class obtained by combining the conceptually complementary pseudo‐natural product (pseudo‐NP) design strategy and a formal adaptation of the complexity‐to‐diversity ring distortion approach. Fragment‐sized α‐methylene‐sesquiterpene lactones, whose scaffolds can formally be viewed as related to each other or are obtained by ring distortion, were combined with alkaloid‐derived pyrrolidine fragments by means of highly selective stereocomplementary 1,3‐dipolar cycloaddition reactions. The resulting pseudo‐sesquiterpenoid alkaloids were found to be both chemically and biologically diverse, and their biological performance distinctly depends on both the structure of the sesquiterpene lactone‐derived scaffolds and the stereochemistry of the pyrrolidine fragment. Biological investigation of the compound collection led to the discovery of a novel chemotype inhibiting Hedgehog‐dependent osteoblast differentiation<br />The combination of the conceptually complementary formal ring distortion‐ and pseudo‐natural product strategies yields novel natural product‐inspired bioactive pseudo‐sesquiterpenoid alkaloids.
- Subjects :
- Stereochemistry
Ring (chemistry)
Catalysis
Pyrrolidine
Cell Line
pseudo-natural products
Mice
chemistry.chemical_compound
Alkaloids
Distortion
Animals
Research Articles
cycloaddition
Biological evaluation
Biological Products
Osteoblasts
Natural product
Molecular Structure
Chemistry
Cell Differentiation
Stereoisomerism
General Chemistry
General Medicine
Highly selective
Cycloaddition
stereodivergent synthesis
Product (mathematics)
ring distortion
Pseudo‐Natural Products
Sesquiterpenes
Research Article
Subjects
Details
- ISSN :
- 15213757 and 00448249
- Volume :
- 133
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie
- Accession number :
- edsair.doi.dedup.....d3036f0e112791f7e2a035b451978c48