Antineoplastic agents. 560. Isolation and structure of kitastatin 1 from an Alaskan Kitasatospora sp

J Nat Prod. 2007 Jul;70(7):1069-72. doi: 10.1021/np068072c. Epub 2007 Jul 4.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / chemistry*
  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / isolation & purification
  • Antineoplastic Agents* / pharmacology
  • Bacteria / drug effects
  • Candida albicans / drug effects
  • Depsipeptides* / chemistry
  • Depsipeptides* / isolation & purification
  • Depsipeptides* / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Leukemia P388
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure

Substances

  • Antineoplastic Agents
  • Depsipeptides
  • kitastatin 1
  • respirantin