A Biomimetic Approach for Polyfunctional Secocholanes: Tuning Flexibility and Functionality on Peptidic and Macrocyclic Scaffolds Derived from Bile Acids

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• 作者：Daniel G. Rivera ; Orlando Pando ; Rayser Bosch ; Ludger A. Wessjohann
• 刊名：Journal of Organic Chemistry
• 出版年：2008
• 出版时间：August 15, 2008
• 年：2008
• 卷：73
• 期：16
• 页码：6229-6238
• 全文大小：375K
• 年卷期：v.73,no.16(August 15, 2008)
• ISSN：1520-6904

文摘

Bile acids are important scaffolds in medicinal and supramolecular chemistry. However, the use of seco bile acids, i.e., bile acids with opened rings, as cores or building blocks for the assembly of complex peptide conjugates or macrocycles has remained elusive so far. A biomimetic approach to secocholanes, based on an oxidative ring-expansion/ring-opening sequence, offers efficient access to novel structures with tunable flexibility and functionality. The process preserves selected portions of the original stereochemical and functional information of the steroid, while additional structural elements are incorporated in further (diversity-generating) steps. The potential of these building blocks for peptide and macrocycle chemistry is exemplified by the attachment of relevant α-amino acids and by the production of various complex macrocycles obtained by conventional (e.g., macrolactonization and macrolactamization) and multicomponent (e.g., Ugi four-component) macrocyclizations. This combination of secocholanic skeleton manipulation with, e.g., varied types of macrocyclization protocols, produces high levels of skeletal diversity and complexity. Therefore, this approach may have applicability either for the synthesis of biologically active ligands or as artificial receptors (“hosts”).