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

2007; American Chemical Society; Volume: 70; Issue: 7 Linguagem: Inglês

10.1021/np068072c

1520-6025

George R. Pettit, Rui Tan, Robin K. Pettit, Thomas H. Smith, Song Feng, Dennis L. Doubek, Linda Richert, John Hamblin, Christine A. Weber, Jean‐Charles Chapuis,

Synthesis and Biological Activity

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 microg/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.