Modular Approaches to Lankacidin Antibiotics
Lingchao Cai1,2, Yanmin Yao2, Seul Ki Yeon2
1Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jinagsu Key Lab of Biomass-Based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing, 210037 Jiangsu, China.
Journal of the American Chemical Society
|August 14, 2020
Summary
Synthetic chemistry advances access to novel lankacidin antibiotics. This study corrects structures of known compounds and creates new derivatives with potential antimicrobial activity.
Area of Science:
- Natural Products Chemistry
- Synthetic Organic Chemistry
- Medicinal Chemistry
Background:
- Lankacidins are polyketide natural products from *Streptomyces spp.* with antimicrobial potential.
- Their complex structures and instability pose challenges for synthesis and modification.
- Previous structural assignments for some lankacidins were inaccurate.
Purpose of the Study:
- To develop novel synthetic routes for lankacidins.
- To generate structurally diverse lankacidin derivatives for stability and activity.
- To correct and confirm the structures of specific lankacidin natural products.
Main Methods:
- Development of three distinct total synthesis strategies for lankacidins.
- Systematic generation of stereochemical variants of cyclic and acyclic lankacidins.
- Synthesis of C4-methylated lankacidins to enhance chemical stability.
Main Results:
- Successful synthesis of diverse lankacidin analogues, including C4-methylated derivatives.
- Correction of the previously reported structures for 2,18-seco-lankacidinol B and iso-lankacidinol.
- Evaluation of the antibacterial and protein translation inhibitory activities of novel lankacidins.
Conclusions:
- The developed synthetic routes provide access to new lankacidin structural variations.
- This work clarifies the structural identity of key lankacidin natural products.
- The generated derivatives offer a platform for developing improved antimicrobial agents.
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