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09:27
Rapid One-step Enzymatic Synthesis and All-aqueous Purification of Trehalose Analogues
Published on: February 17, 2017
Total synthesis of etnangien
Pengfei Li1, Jun Li, Fatih Arikan
1Institut für Organische Chemie, Ruprecht-Karls-Universität Heidelberg, INF 270, D-69120 Heidelberg, Germany.
Journal of the American Chemical Society
|August 4, 2009
Summary
Researchers report the first total synthesis of etnangien, a potent RNA-polymerase inhibitor. This study clarifies the macrolide antibiotic
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Molecular Biology
Background:
- Etnangien is a potent inhibitor of RNA-polymerase.
- The macrolide antibiotic's complex structure and stereochemistry present a significant synthetic challenge.
Purpose of the Study:
- To achieve the first total synthesis of etnangien.
- To unequivocally establish the relative and absolute configuration of etnangien.
- To develop a modular and efficient synthetic route amenable to analogue design.
Main Methods:
- Stereoselective substrate-controlled boron- and tin-mediated aldol couplings to construct stereogenic centers.
- Heck macrocyclization of a conformationally restricted substrate for ring formation.
- Late-stage introduction of a labile side chain.
Main Results:
- Successful completion of the first total synthesis of etnangien.
- High stereoselectivity and yield achieved in aldol coupling reactions.
- Efficient macrocyclization and late-stage functionalization were demonstrated.
Conclusions:
- The described synthetic strategy unequivocally establishes the configuration of etnangien.
- The convergent and modular approach facilitates the synthesis of designed analogues.
- This work provides a foundation for further exploration of etnangien's biological activity and derivatives.
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