1. Total synthesis and a systematic structure-activity relationship study of WAP-8294A2.
- Author
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Chen, Delin, Tian, Liwen, Po, Kathy Hiu Laam, Chen, Sheng, and Li, Xuechen
- Subjects
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STRUCTURE-activity relationships , *GRAM-positive bacteria , *PEPTIDE antibiotics , *ALANINE , *MACROCYCLIC compounds - Abstract
WAP-8294A2 is a cyclic peptide antibiotic with novel structure and excellent activity against Gram-positive pathogens. Herein, we report the total synthesis of complex macrocyclic peptide WAP-8294A2 (W 1) , ent -analogue W 2 , deoxy analogue W 3 and de-methyl analogue W 4 using a solid-phase synthetic route followed by a final stage solution-phase cyclization reaction. Exploitation of this process allowed the synthesis of eleven alanine-scanning analogues and eight lysine-scanning analogues. The antimicrobial activity of these analogues was evaluated in vitro against Gram-positive bacteria. Based on the MIC results, a primary systematic structure-activity relationship has been established. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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