The structure of Palau'amide, a potent cytotoxin from a species of the marine cyanobacterium Lyngbya.
Bioassay-guided fractionation of the extract of a species of Lyngbya from Palau has yielded Palau'amide (1), which had an IC(50) value of 13 nM against KB cells. The structure of 1 was elucidated by NMR analysis in a variety of solvents. In particular, a gradient-enhanced band-selective HMBC experiment allowed unambiguous assignment of HMBC correlations to carbon signals that were separated by 0.1 ppm. The relative stereochemistry and the absolute configurations of all but one (C-37) of the nine chiral centers were determined by NMR analysis of the alpha-methoxyphenylacetic acid (MPA) derivatives and chiral HPLC of the degradation products of 1. The assignment of S rather than R stereochemistry at C-37 is discussed in detail.
Williams
Philip G
PG
Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA.
Yoshida
Wesley Y
WY
Quon
Michael K
MK
Moore
Richard E
RE
Paul
Valerie J
VJ
D000458:Cyanobacteria / Q000737:chemistry*; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells / Q000187:drug effects; D008235:Lyngbya Toxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D019029:Palau; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D003603:Cytotoxins; D008235:Lyngbya Toxins; D010456:Peptides, Cyclic; C482752:palauamide