Kulokekahilide-1, a cytotoxic depsipeptide from the cephalaspidean mollusk Philinopsis speciosa.

Abstract

The cytotoxic depsipeptide kulokekahilide-1, which contains two unusual amino acids, 4-phenylvaline and 3-amino-2-methylhexanoic acid, was isolated from the cephalaspidean mollusk Philinopsis speciosa. Structure elucidation of kulokekahilide-1 was carried out by spectroscopic analysis and chemical degradation. The absolute stereochemistry was determined by Marfey analysis for amino acids and chiral HPLC analysis for hydroxy acids. All four stereoisomers of 4-phenylvaline and 3-amino-2-methylhexanoic acid, which were necessary for Marfey analysis, were synthesized by use of the Heck reaction and Evans's method, respectively. Kulokekahilide-1 showed cytotoxicity against P388 murine leukemia cells with an IC(50) value of 2.1 microg/mL.

• Authors: Junji Kimura, Yuuki Takada, Tomoko Inayoshi, Yoichi Nakao, Gilles Goetz, Wesley Y Yoshida, Paul J Scheuer
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 67 Issue 6 Pg. 1760-7 (Mar 22 2002) ISSN: 0022-3263 [Print] United States
• PMID: 11895390 (Publication Type: Journal Article)

Chemical References

• 3-amino-2-methylhexanoic acid
• 4-phenylvaline
• Aminocaproates
• Antineoplastic Agents
• Caproates
• Depsipeptides
• Peptides, Cyclic
• dolastatin 16
• kulokekahilide-1
• Valine

Topics

• Amino Acid Sequence
• Aminocaproates
• Animals
• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Caproates (chemical synthesis, chemistry)
• Chromatography, High Pressure Liquid
• Depsipeptides
• Drug Screening Assays, Antitumor
• Hawaii
• Inhibitory Concentration 50
• Leukemia P388
• Mice
• Mice, Inbred Strains
• Molecular Conformation
• Molecular Structure
• Mollusca (chemistry)
• Nuclear Magnetic Resonance, Biomolecular
• Peptides, Cyclic (chemistry, isolation & purification, pharmacology)
• Stereoisomerism
• Valine (analogs & derivatives, chemical synthesis)