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.