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: 3.8). 11/2011; 74(11):2332-7. DOI: 10.1021/np200205n
Source: PubMed


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.

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    • "Eighteen lanostanoids (1–18) (Fig. 1) were isolated from H. longipes of which nine (1–9) were new. The known compounds 10–18 were identified as ganoderiol D (10) (Nishitoba et al., 1988), lanosta-8-en-7-one-3b-acetyloxy-24,25,26-trihydroxy (11) (Fujita et al., 1986), ganodermanondiol (12) (Fujita et al., 1986), lucidumol B (13) (Fujita et al., 1986), 26-hydroxy-ganodermanon- diol (14) (Kennedy et al., 2011), lucidadiol (15) (Gonzalez et al., 1999), lucidadone H (16) (Nishitoba et al., 1987), lucidadone A (17) (Nishitoba et al., 1985), and lanosta-7,9(11),24E-trien-26-al- 3-oxo (18) (Gonzalez et al., 2002) by comparison of their NMR spectroscopic data with those reported in the literature. "
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    ABSTRACT: Nine lanostanoids, together with nine known ones, were isolated from the ethyl acetate extract of the fruiting bodies of the mushroom Haddowia longipes. Their structures were elucidated as 11-oxo-ganoderiol D, lanosta-8-en-7,11-dioxo-3β-acetyloxy-24,25,26-trihydroxy, lanosta-8-en-7-oxo-3β-acetyloxy-11β,24,25,26-tetrahydroxy, lanosta-7,9(11)-dien-3β-acetyloxy-24,25,26-trihydroxy, lanosta-7,9(11)-dien-3β-acetyloxy-24,26-dihydroxy-25-methoxy, 11-oxo-lucidadiol, 11β-hydroxy-lucidadiol, lucidone H and lanosta-7,9(11),24E-trien-3β-acetyloxy-26,27-dihydroxy by analysing their 1D/2D NMR and MS spectra. In addition, bioassays of inhibitory activity against acetylcholinesterase (AChE) of all compounds showed that thirteen compounds possessed inhibitory activity against AChE with the percentage inhibition ranging from 10.3% to 42.1% when tested at 100 μM.
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