Concise Synthesis and Antimicrobial Evaluation of the Guanidinium Alkaloid Batzelladine D: Development of a Stereodivergent Strategy
| Autor: | Aubert Ribaucourt, Joshua G. Pierce, Yasamin Moazami, You-Chen Lin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Staphylococcus aureus
Stereochemistry Molecular Conformation Stereoisomerism Microbial Sensitivity Tests 010402 general chemistry 01 natural sciences Biochemistry Article Catalysis Pyrrolidine chemistry.chemical_compound Alkaloids Colloid and Surface Chemistry Bicyclic molecule Extramural Alkaloid Late stage General Chemistry Batzelladine D Antimicrobial Anti-Bacterial Agents 0104 chemical sciences Pyrimidines chemistry |
| Zdroj: | J Am Chem Soc |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.0c04091 |
| Popis: | Herein, we describe a stereodivergent route to (±)-batzelladine D (2), (+)-batzelladine D (2), (−)-batzelladine D (2), and a series of stereochemical analogues and explore their antimicrobial activity for the first time. The concise synthetic approach enables access to the natural products in a sequence of 8–12 steps from readily available building blocks. Highlights of the synthetic strategy include gram-scale preparation of a late stage intermediate, pinpoint stereocontrol around the tricyclic skeleton, and a modular strategy that enables analogue generation. A key bicyclic β-lactam intermediate not only serves as the key controlling element for pyrrolidine stereochemistry but also serves as a preactivated coupling partner to install the ester side chain. The stereocontrolled synthesis allowed for the investigation of the antimicrobial activity of batzelladine D, demonstrating promising activity that is more potent for non-natural stereoisomers. |
| Databáze: | OpenAIRE |
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