Antineoplastic Agents 560. Isolation and Structure of Kitastatin 1 from an Alaskan Kitasatospora sp.1

• Published in: Journal of Natural Products
• Main Authors: Pettit, George R., Tan, Rui, Pettit, Robin K., Smith, Thomas H., Feng, Song, Doubek, Dennis L., Richert, Linda, Hamblin, John, Weber, Christine, Chapuis, Jean-Charles
• Format: Text
• Language: English
• Published: 2007
• Subjects: Article; Beaufort Sea; Tundra
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596607; http://www.ncbi.nlm.nih.gov/pubmed/17608530; https://doi.org/10.1021/np068072c

By utilizing a bioassay-guided separation (P388 lymphocytic leukemia and a panel of human cancer cell lines) of fermentation broths from a Kitasatospora sp. collected from a tundra soil sample taken at the shore of the Beaufort Sea, we have isolated three powerful (GI50 to 0.0006 μg/mL) cancer cell growth inhibitors (1-3) and determined their structures to be closely related cyclodepsipeptides. From 380-L fermentations of Kitasatospora sp. were obtained 2.6 mg of a new cyclodepsipeptide designated kitastatin 1 (3), accompanied by the previously known respirantin (1, 10.8 mg) and its valeryl homologue (2, 4.8 mg). The structures were determined by employment of a series of high-resolution mass and 2D-NMR spectroscopic analyses. The stereochemical assignments and overall structures were confirmed by subsequent total synthesis of depsipeptide 1, as reported in the accompanying contribution.