Antineoplastic Agents. 560. Isolation and Structure of Kitastatin 1 from an Alaskan Kitasatospora sp.1
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By utilizing a bioassay-guided separation (P388 lymphocytic leukemia and a panel of human cancer cell lines) offermentation 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 g/mL) cancer cell growth inhibitors (1-3) and determined their structuresto be closely related cyclodepsipeptides. From 380 L fermentations of Kitasatospora sp. were obtained 2.6 mg of a newcyclodepsipeptide designated kitastatin 1 (3), accompanied by the previously known respirantin (1, 10.8 mg) and itsvaleryl homologue (2, 4.8 mg). The structures were determined by employment of a series of high-resolution mass and2D NMR spectroscopic analyses. The stereochemical assignments and overall structures were confirmed by subsequenttotal synthesis of depsipeptide 1, as reported in the accompanying contribution.

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