Neutron diffraction structure of melampodin: its role in the reclassification of the germacranolides

The precise crystal and molecular structure of melampodin, C(21)H(24)O(9), was determined from three-dimensional neutron diffraction data collected by counter techniques and phases by direct statistical methods. Crystals are orthorhombic, P2(1)2(1)2(1), a = 8,990(9), b = 14.352(14), c = 16.294(16) A, V = 2102 A(3), d(calc.) = 1.328 g.cm(-3), Z = 4 molecules per unit cell. The structural model was refined by full matrix least-squares of 2303 observed independent reflections, with all 54 atoms treated anisotropically, to R(F) = 5.0%. Hydrogen bonds link melampodin molecules together in the solid state. The conformation of the cyclodeca-1,5-diene ring is such that one intraannular hydrogen atom interacts strongly with one double bond, but there is little or no transannular interaction between double bonds. Strain in the ten-membered ring and in the trans-fused lactone ring is discussed, as are chemical implications of the unsymmetric epoxide in the epoxyangelic acid side chain. The previously suggested reclassification of germacranolide sesquiterpene lactones into four subgroups is supported, and a new convention for configurational representations of the four subgroups is proposed.