Structural and conformational studies on sesquiterpenoids Part II: X-ray, molecular mechanics and NMR analysis of slovanolides

Abstract

The crystal structures of the slovanolide 3 and of the 0(6)-monoacetate of its base-catalysed rearrangement product ( 7) are reported. These compounds differ for the closure of the γ-lactone ring (C(6)- cis versus C(8)- trans), and display a different conformation in the solid state; in both molecules the seven-membered ring assumes a twist-chair (TC) conformation, but with the approximate C 2 through C(7) in 3 and through C(5) in 7. The 1H NMR spectra indicate that these differences are also maintained in solution, where no rotameric equilibrium is present. Molecular-mechanics calculations have been carried out on several model compounds. In particular, calculations on the bis-γ-hydroxyacid 8 formed upon treatment with bases of 3 and 7, showed that the C(5)-TC conformation is more stable by about 8 kcal mol −1 and that intramolecular hydrogen bonds and, to a lesser extent, ring torsional strain, are the main cause of its stabilisation. It was also shown that lactonisation of the hydroxyacid 8 from the C(5)-TC conformation can only take place at C(8), whereas lactonisation at C(6) is only attainable from the C(7)-TC conformation. The exclusive lactonisation at C(8) reflects therefore the overwhelming preference of the bis-γ-hydroxyacid for the C(5)-TC conformation. The interconversion pathway betwewen the C(7)-and C(5)-TC conformations of the bis-γ-hydroxyacid has also been analysed. Only two minima are found, separated by a large energy barrier, corresponding to the TC conformation of lactones 3 and 7.