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Total synthesis of herbimycin A
Rui Yan1, Chuancai Bian, Xiaoming Yu
1State Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences , No. 1 Xiannongtan Street, Beijing 100050, China.
Organic Letters
|June 10, 2014
Summary
Researchers synthesized the benzoquinone ansamycin antibiotic herbimycin A using a novel chiral γ-lactone synthon. This efficient catalytic asymmetric synthesis strategy simplifies access to stereogenic centers and aids molecular editing of related compounds.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Synthetic Chemistry
Background:
- Benzoquinone ansamycins are a class of antibiotics with significant biological activity.
- Herbimycin A is a prominent member of this class, known for its antitumor properties.
- Efficient synthesis of complex natural products like herbimycin A is crucial for drug discovery and development.
Purpose of the Study:
- To develop a novel and efficient synthetic route for herbimycin A.
- To design a key chiral synthon for constructing the complex ansamycin core.
- To establish a versatile strategy for the molecular editing of benzoquinone ansamycins.
Main Methods:
- A 19-step linear synthesis was employed.
- A chiral γ-lactone was designed as a C11-C15 synthon.
- Catalytic asymmetric synthesis was utilized for the C8-C20 fragment.
- The strategy focused on facile access to stereogenic centers.
Main Results:
- Herbimycin A was synthesized with an overall yield of 4.2%.
- The designed chiral γ-lactone enabled a facile catalytic asymmetric synthesis of the C8-C20 fragment.
- The synthetic strategy provided easy access to crucial stereogenic centers.
- The overall yield was considered high for such a complex molecule.
Conclusions:
- The developed synthetic strategy is efficient and applicable to benzoquinone ansamycin synthesis.
- The chiral γ-lactone synthon is a key innovation for accessing complex ansamycin structures.
- This approach facilitates molecular editing and potential development of new herbimycin A analogs.