Total synthesis and antimicrobial evaluation of natural albomycins against clinical pathogens

  • Nat Commun. 2018 Sep 4;9(1):3445. doi: 10.1038/s41467-018-05821-1.
Zihua Lin  1 ,  Xiaobo Xu  1  2 ,  Sheng Zhao  1 ,  Xiaohong Yang  1 ,  Jian Guo  1 ,  Qun Zhang  3 ,  Chunmei Jing  3 ,  Shawn Chen  4 ,  Yun He  5
Affiliations
  • 1. Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, 55 Daxuecheng South Road, 401331, Shapingba, Chongqing, China.
  • 2. College of Chemistry and Pharmaceutical Engineering, Huanghuai University, 463000, Zhumadian, China.
  • 3. Medicine Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, 400014, Yuzhong, Chongqing, China.
  • 4. Global Health Drug Discovery Institute, School of Pharmaceutical Sciences, Tsinghua University, 30 Shuangqing Rd, 100084, Haidian, Beijing, China.
  • 5. Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, 55 Daxuecheng South Road, 401331, Shapingba, Chongqing, China. [email protected].
PMID: 30181560 DOI: 10.1038/s41467-018-05821-1
Abstract

Development of effective antimicrobial agents continues to be a great challenge, particularly due to the increasing resistance of superbugs and frequent hospital breakouts. There is an urgent need for more potent and safer Antibiotics with novel scaffolds. As historically many commercial drugs were derived from natural products, discovery of antimicrobial agents from complex natural product structures still holds a great promise. Herein, we report the total synthesis of natural albomycins δ1 (1a), δ2 (1b), and ε (1c), which validates the structures of these peptidylnucleoside compounds and allows for synthetic access to bioactive albomycin analogs. The efficient synthesis of albomycins enables extensive evaluations of these natural products against model bacteria and clinical pathogens. Albomycin δ2 has the potential to be developed into an Antibacterial drug to treat Streptococcus pneumoniae and Staphylococcus aureus infections.

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