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Synlett 2025; 36(12): 1770-1774
DOI: 10.1055/a-2589-5573
DOI: 10.1055/a-2589-5573
letter
Semi-Synthesis of (+)-Digitoxigenin: Selective Bromination for Construction of the Key Intermediate
This work was financially supported by the National Key Research and Development Program of China (2023YFC2308200), the National Natural Science Foundation of China (82373710), the State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture (NZYSKL240204), and the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine (ZYXJC2024-006).
Abstract
A concise and scalable semi-synthesis of (+)-digitoxigenin (1) has been accomplished in nine linear steps. This route features the construction of the C(15)=C(16) double bond in intermediate 6 via selective C16 bromination followed by elimination. Subsequesntly, a single-step SeO2 oxidation directly installed the C14-β-hydroxyl group, producing 7. This strategy avoids precious metals, greatly reduces synthesis costs, and can be extended to the synthesis of related cardiotonic steroids.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2589-5573.
- Supporting Information
Publication History
Received: 03 April 2025
Accepted after revision: 16 April 2025
Accepted Manuscript online:
16 April 2025
Article published online:
27 May 2025
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