Planta Med 2013; 79 - P46
DOI: 10.1055/s-0033-1336488

Enantioselective Synthesis of (-)-Laurenditerpenol

P Peddikotla 1, AG Chittiboyina 1, MA Avery 2, IA Khan 1, 3
  • 1National Center for Natural Products Research
  • 2Department of Medicinal Chemistry
  • 3Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, USA

Laurenditerpenol [1] is the first marine natural product to inhibit hypoxia-inducible factor-1 (HIF-1) activation; preclinical studies support the inhibition of HIF-1 as a major molecular target for antitumor drug discovery. In 2007 [2], the ambiguity in absolute chemistry of natural laurenditerpenol had been resolved by synthesizing the six isomers out of eight conceivable isomers of laurenditerpenol by our research group as (-)-(1S,6R,7S,10R,11R,14S,15R)-laurenditerpenol. Herein we report enantio-selective synthesis of (-)-laurenditerpenol involving asymmetric “anion assisted” Diels-Alder reaction/sequential Michael addition, sulfone assisted hydroboration as key reaction steps. The full synthetic details chemical transformations along with key reactions will be presented.

Acknowledgements: This study was supported in part by United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement No. 58 – 6408 – 02 – 1-612. References: [1] Mohammed KA, Hossain CF, et al. (2004)J Nat Prod, 67: 2002 – 2007. [2] Chittiboyina AG, Kumar, GM, et al. (2007)J Med Chem, 50: 6299 – 6302.