Modular Synthesis of the Potent Antibiotic Amycolamicin and Diastereomeric Analogues Thereof
A modular approach to the potent, broad-spectrum antibiotic amycolamicin and seven diastereomeric analogues is described. The synthesis features bioinspired construction of the high-carbon amycolose segment, gold(I)-catalyzed high-yielding <i>O</i>-glycosylation of the <i>trans</i>-decalin scaffold, <i>N</i>-glycosylation of the bromoacetylated l-valine derivative, and condition-tuned late-stage <i>C</i>-acylation of the tetramic acid motif. An assessment of the antibacterial properties of these synthetic molecules indicated that the correct stereochemistry is essential for the potent bioactivity of amycolamicin.
Authors
- Cai‐Guang Yang (ORCID: https://orcid.org/0000-0001-5778-4422)
- Peng Hui Xu (ORCID: https://orcid.org/0000-0002-9593-7167)
- Xuejian Yin
- Qiuyu Zhu (ORCID: https://orcid.org/0000-0001-9514-9323)
- Biao Yu (ORCID: https://orcid.org/0000-0002-3607-578X)
- Dapeng Zhu (ORCID: https://orcid.org/0000-0001-9049-8209)
- Ziqi Yuan (ORCID: https://orcid.org/0000-0003-2397-2163)
- Zhengxuan Zhang (ORCID: https://orcid.org/0000-0002-8807-4375)
Institutions
- Shanghai Jiao Tong University (CN)
- ShanghaiTech University (CN)
- Shanghai Institute of Materia Medica (CN)
- Shanghai Institute of Organic Chemistry (CN)
- Center for Translational Molecular Medicine (NL)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-04-02
- DOI
- https://doi.org/10.1021/acs.orglett.5c00742
- Citations
- 2
- Primary Topic
- Chemical Synthesis and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Shanghai Jiao Tong University
- National Key Research and Development Program of China