Piperapeptins A and B, Cyclic Hexapeptides Containing the Rare Amino Acid Piperazic Acid, Produced by a Combined-Culture of Amycolatopsis sp. and Tsukamurella pulmonis

The novel cyclic hexapeptides, piperapeptins A (1) and B (2) with rare N−OH-Leu and piperazic acid moieties, were discovered in the combined-culture broth of Amycolatopsis sp. 26-11 and Tsukamurella pulmonis TP-B0596. The planar structures were elucidated by HR-MS and 1D/2D NMR analyses. The stereochemistry of Ala and Phe was determined using our highly sensitive advanced Marfey’s method. The structures of N-OH-Leu, piperazic acids, and 4-OH-piperazic acids were confirmed by single-crystal X-ray diffraction analysis. Piperapeptins A (1) and B (2) exhibited weak antibacterial activity against Bacillus subtilis, and 1 showed an IC50 value of 14.9 ± 3.9 μM against HeLa S3 cells.