Antineoplastic agents. 560. Isolation and structure of kitastatin 1 from an Alaskan Kitasatospora sp.
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.
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, PO Box 872404, Tempe, Arizona 85287-2404, USA. bpettit@asu.edu
Tan
Rui
R
Pettit
Robin K
RK
Smith
Thomas H
TH
Feng
Song
S
Doubek
Dennis L
DL
Richert
Linda
L
Hamblin
John
J
Weber
Christine
C
Chapuis
Jean-Charles
JC
D039903:Actinobacteria / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007941:Leukemia P388; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure
D000970:Antineoplastic Agents; D047630:Depsipeptides; C521973:kitastatin 1; C081425:respirantin