Zelkovamycins F and G, Cyclopeptides with Cα-Methyl-threonine Residues, from an Endophytic <i>Kitasatospora</i> sp.
Xiaomeng Hao, Shasha Li, Guiyang Wang, Jianrui Li, Zong‐Gen Peng, Yu‐Qin Zhang, Liyan Yu, Maoluo Gan
Abstract
Zelkovamycins F and G (1 and 2), two new natural cyclic octapeptides possessing the unprecedented nonproteinogenic amino acid residues l-α-methyl-threonine and l-α-methyl-allo-threonine, respectively, along with four new analogues, zelkovamycins H–K (3–6), were identified from the endophytic Kitasatospora sp. CPCC 204717. Their structures were elucidated by detailed analysis of NMR and HRESIMS/MS spectroscopic data. The configurations of amino acid residues were determined by Marfey’s analysis combined with NMR calculations. Compounds 1, 2, and 4 showed potent antibacterial activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. The structure–activity relationship study revealed that the 2-methyl-3-oxobutyrine and sarcosine residues played important roles in their antibacterial activities. Zelkovamycin (7) and zelkovamycin E (8) exhibited significant antiviral activity against the hepatitis C virus.