Semisynthesis and Biological Evaluation of Ganodermanontriol and Its Stereoisomeric Triols

Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, Indiana 46202, USA.
Journal of Natural Products (Impact Factor: 3.95). 11/2011; 74(11):2332-7. DOI: 10.1021/np200205n
Source: PubMed

ABSTRACT The first synthesis of ganodermanontriol, a bioactive lanostane triterpene from the medicinal mushroom Ganoderma lucidum, has been achieved in 15.3% yield over nine steps, along with its three stereoisomeric triols and ganoderol A. The key steps leading to this family of isomers involve the reconstruction of the trisubstituted alkene by stereoselective and chemoselective phosphonate reactions and the formation of the unusual Δ7,9(11)-diene core by the mild acidic opening of a lanosterone-derived epoxide. Ganodermanontriol showed promising activity on the inhibition and proliferation of breast cancer cells. The effect of ganodermanontriol and its isomers on cell proliferation was assayed; IC50 values of 5.8 and 9.7 μM on breast cancer cell lines MCF-7 and MDA-MB-231, respectively, were found for ganodermanontriol.