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Total Synthesis of (+)-Rubellin C
Jackson A Gartman1, Uttam K Tambar1
1Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
Organic Letters
|August 19, 2020
Summary
Researchers achieved the first stereoselective synthesis of rubellin C, a complex molecule targeting Alzheimer's disease. This breakthrough in total synthesis opens new avenues for developing therapies against tau protein aggregation.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Neuroscience
Background:
- Rubellins are complex anthraquinoid heterodimers with a unique chemical scaffold.
- Despite being known for over 30 years, no total synthesis of rubellins has been reported.
- Rubellin's structure is implicated in inhibiting and reversing tau protein aggregation, a key factor in Alzheimer's disease.
Purpose of the Study:
- To achieve the first stereoselective total synthesis of a rubellin family member.
- To develop a synthetic strategy for constructing the complex topology and stereochemistry of rubellins.
- To provide a foundation for further research into rubellin derivatives as potential Alzheimer's disease therapeutics.
Main Methods:
- Employed strategic disconnections for efficient synthesis planning.
- Utilized borylative reactions and transition metal-catalyzed steps.
- Completed the synthesis in a concise 16-step sequence.
Main Results:
- Successfully synthesized (+)-rubellin C with stereochemical control.
- Demonstrated the feasibility of constructing the intricate 6-5-6 fused ring system.
- Achieved the synthesis of a molecule with five neighboring stereocenters, including a quaternary center.
Conclusions:
- This study reports the first stereoselective total synthesis of (+)-rubellin C.
- The developed synthetic route is efficient and allows for the construction of complex molecular architectures.
- The synthesis provides access to rubellins for further investigation into their therapeutic potential for Alzheimer's disease.
