Zelkovamycins F and G, Cyclopeptides with Cα-Methyl-threonine Residues, from an Endophytic Kitasatospora sp.

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.