Total Synthesis and Biological Evaluation of the Antibiotic Lysocin E and Its Enantiomeric,Epimeric, and N‐Demethylated Analogues |
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| Authors: | Dr. Motoki Murai Takuya Kaji Dr. Takefumi Kuranaga Dr. Hiroshi Hamamoto Prof. Dr. Kazuhisa Sekimizu Prof. Dr. Masayuki Inoue |
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| Affiliation: | Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐0033 (Japan) |
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| Abstract: | Lysocin E, a macrocyclic peptide, exhibits potent antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA) through a novel mechanism. The first total synthesis of lysocin E was achieved by applying a full solid‐phase strategy. The developed approach also provides rapid access to the enantiomeric, epimeric, and N‐demethylated analogues of lysocin E. Significantly, the antibacterial activity of the unnatural enantiomer was comparable to that of the natural isomer, suggesting the absence of chiral recognition in its mode of action. |
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| Keywords: | antibiotics natural products solid‐phase synthesis structure– activity relationships total synthesis |
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