Macrocyclic Pyrrolizidine Alkaloids and Silphiperfolanol Angelate Esters from Solanecio mannii

Three new compounds, the silphiperfolanol angelate ester umutagarananol ( 1 ), the macrocyclic pyrrolizidine alkaloids umutagarinine A and B ( 2 – 3 ), and five known secondary metabolites ( 4 – 8 ) were isolated from the CH₂Cl₂−MeOH (1 : 1) extract of the roots and the stem bark of Solanecio mannii (Hook. f.) (Asteraceae). The isolated compounds were characterized by NMR and IR spectroscopic, and mass spectrometric analyses, whereas the relative stereochemistry of 4 was established by NAMFIS-based combined computational and solution NMR analysis. Synthetic modification of 5 provided two new compounds, 2-angeloyloxy-4,8-epoxypresilphiperfolane ( 9 ) and 2-angeloyloxy-4,8-epoxypresilphi-perfolane ( 10 ). The crude extracts and the isolated constituents showed weak antibacterial activities (EC₅₀ 0.7–13.3 mM) against the Gram-negative Escherichia coli and the Gram-positive Bacillus subtilis. Compounds 2 , 3 and 4 exhibited strong cytotoxicity against MCF-7 human breast cancer cells, with EC₅₀ values of 35.6, 21.7 and 12.5 μM, respectively.     

Conformational properties of the macrocyclic trichothecene mycotoxin verrucarin A in solution

Phase-sensitive nuclear Overhauser enhancement spectroscopy (NOESY) experiments, (3)J couplings and computational molecular modeling (MM2* and MMFF force fields) were employed to examine the conformational properties of verrucarin A in chloroform solutions. The MMFF force field calculations resulted in a family of 12 low-energy structures along with their populations, the latter being determined by the NMR analysis of molecular flexibility in solution(NAMFIS) deconvolution analysis. The concluded model was capable of reproducing successfully the experimental NOESY cross-peak volumes and the proton-coupling constants. Among the 12 conformers, the one which was similar to the structure of verrucarin A in the solid state was the predominant accounting for 75% of the total relative population, although other low-energy conformations contributed to a lesser degree in order to explain the experimental data.