Planta Med 2014; 80 - PK1
DOI: 10.1055/s-0034-1382633

Karlotoxin 5 synthetic studies: Concise synthesis of a C91 – 17) polyol chain fragment

M Albadry 1, 2, A Waters 1, T Tomioka 3, MT Hamann 1
  • 1Departments of Pharmacognosy, Pharmacology, Chemistry and Biochemistry and National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA
  • 2Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
  • 3Department of Chemistry and Biochemistry, University of Mississippi, University, MS 38677, USA

Karlotoxins, a group of dinoflagellate derived polyketides, have attracted much attention as potential therapeutic compounds due to their unique MoA and selective cytotoxic activities against leukemia and lung cancer in the NCI60 panel. The richly oxygenated C (1 – 17) polyol chain of karlotoxin 5 has been synthesized. Incorporated in this long chain are 6 of the 28 stereogenic centers housed in the target compound. The asymmetric pathway that has been developed is based on repeating a three-step chain elongation strategy consisting of (i) simultaneous reductive O-debenzylation and hydrogenation of alkene with Pd/C catalyst, (ii) oxidation of alcohol, and (iii) Julia-Kocienski olefination.

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