Stereochemical Analysis of Leubethanol, an Anti-TB-Active Serrulatane, from Leucophyllum frutescens

Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi-drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25-12.50 mu g/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, from H-1 NMR full spin analysis, and by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers.