A Bridge to Alkaloid Synthesis. Issue 1 (2nd September 2021)

• Record Type: Journal Article
• Authors: Zhai, Li; Tang, Ye; Zhang, Yan; Huang, Sha‐Hua; Zhu, Lili; Hong, Ran
• Is Part Of: Chemical record. Volume 22:Issue 1(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-02
• Subjects: alkaloid -- aza-Wacker -- Mannich -- nitroso-ene -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/tcr.202100197
• Languages: English
• ISSNs: 1527-8999

Abstract

Abstract: The construction of a structurally rigid architecture with chiral complexity, necessary to enhance the interaction with binding sites of drug targets, has been adapted as an intriguing approach in drug development. In the past few years, we have been interested in the synthesis of biologically significant and bridged alkaloids via novel synthetic methods and strategies based on recognition of the privileged pattern. Therefore, nitroso‐ene and aza‐Wacker cyclizations were elevated for the first time to construct bridged alkaloids, such as hosieine A, kopsone, melinonine‐E and strychnoxanthine. Mechanistic investigations, including computational calculations for nitroso‐ene reaction and deuterated experiments for aza‐Wacker reaction, enable us to gain more insights into the chemical reactivity and selectivity of specific functional groups in developing viable synthetic methods. Abstract : A Bridge for the Bridge : Developing novel nitroso‐ene and aza‐Wacker cyclizations in the construction of bridged aza‐cycles is summarized in this account. The unique structure of bioactive natural products is a driving force for the discovery of new reaction modality as viable synthetic methods to discern substructural motifs.