Concise Formal Synthesis of the Pseudopterosins via Anionic Oxy-Cope/Transannular Michael Addition Cascade
Vincenzo Ramella1, Philipp C Roosen1, Christopher D Vanderwal1,2
1Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, United States.
Organic Letters
|February 21, 2020
Summary
A novel cascade reaction transforms a Diels-Alder product into the hydrophenalene core of pseudopterosin aglycones. This efficient synthesis provides a direct route to these complex natural product skeletons.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- Pseudopterosins are marine natural products with potential therapeutic applications.
- The synthesis of their complex carbon skeletons presents a significant challenge.
- Spirocyclic architectures offer a unique starting point for complex molecule construction.
Purpose of the Study:
- To develop an efficient synthetic route to the hydrophenalene core of pseudopterosin aglycones.
- To utilize a cascade reaction involving Diels-Alder cycloaddition and anionic oxy-Cope/transannular Michael addition.
- To achieve a short formal synthesis of the target aglycones.
Main Methods:
- Diels-Alder cycloaddition to generate a spirocyclic architecture.
- Anionic oxy-Cope rearrangement followed by transannular Michael addition.
- Oxidation of a cyclohexenone to a phenol.
Main Results:
- Successful conversion of a spirocyclic precursor to the hydrophenalene skeleton.
- Demonstration of a cascade reaction sequence.
- Completion of a short formal synthesis of pseudopterosin aglycones.
Conclusions:
- The developed cascade reaction is an effective method for constructing the pseudopterosin aglycone skeleton.
- This approach offers a concise and efficient route to valuable natural product scaffolds.
- The strategy highlights the utility of spirocyclic intermediates in complex synthesis.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
![Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60786.jpg&w=3840&q=50)
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