Total synthesis and biological evaluation of +-kalkitoxin, a cytotoxic metabolite of the cyanobacterium Lyngbya majuscula.
+-Kalkitoxin, a metabolite of the marine cyanobacterium Lyngbya majuscula, was synthesized from (R)-2-methylbutyric acid, (R)-cysteine, and (3S, 4S, 6S)-3,4,6-trimethyl-8-(methylamino)octanoic acid. A key step in the synthesis was installation of the anti,anti methyl stereotriad by means of a tandem asymmetric conjugate addition of an organocopper species to an alpha,beta-unsaturated N-acyl oxazolidin-2-one followed in situ by alpha-methylation of the resultant enolate. The thiazoline portion of kalkitoxin was assembled by titanium tetrachloride catalyzed cyclization of a vinyl substituted amido thiol.
White
James D
JD
Department of Chemistry, Oregon State University, Corvallis, OR 97331-4003, USA. james.white@oregonstate.edu
Xu
Qing
Q
Lee
Chang-Sun
CS
Valeriote
Frederick A
FA
D002470:Cell Survival / Q000187:drug effects; D000458:Cyanobacteria / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000138:chemical synthesis* / Q000494:pharmacology*; D015394:Molecular Structure; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
D008055:Lipids; D013844:Thiazoles; C121885:kalkitoxin