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
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, PO Box 872404, Tempe, Arizona 85287-2404, USA.
J Nat Prod. 2007 Jul;70(7):1069-72. doi: 10.1021/np068072c. Epub 2007 Jul 4.
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.
通过对从波弗特海沿岸采集的冻原土壤样本中分离得到的北里孢菌属菌株发酵液进行生物测定导向分离（P388淋巴细胞白血病和一组人类癌细胞系），我们分离出了三种强效（GI50至0.0006微克/毫升）的癌细胞生长抑制剂（1 - 3），并确定它们的结构为密切相关的环缩肽。从380升北里孢菌属菌株发酵液中获得了2.6毫克新的环缩肽，命名为北里他汀1（3），同时还得到了先前已知的呼吸素（1，10.8毫克）及其戊酰同系物（2，4.8毫克）。通过一系列高分辨率质谱和二维核磁共振光谱分析确定了其结构。如随附论文所报道，环缩肽1的立体化学归属和整体结构通过随后的全合成得到了证实。
