Structure and absolute configuration of natural fungal product beauveriolide I, isolated from Cordyceps javanica, determined by 3D electron diffraction.

Beauveriolides, including the main beauveriolide I {systematic name: (3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methylpropyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone, C27H41N3O5}, are a series of cyclodepsipeptides that have shown promising results in the treatment of Alzheimer's disease and in the prevention of foam cell formation in atherosclerosis. Their crystal structure studies have been difficult due to their tiny crystal size and fibre-like morphology, until now. Recent developments in 3D electron diffraction methodology have made it possible to accurately study the crystal structures of submicron crystals by overcoming the problems of beam sensitivity and dynamical scattering. In this study, the absolute structure of beauveriolide I was determined by 3D electron diffraction. The cyclodepsipeptide crystallizes in the space group I2 with lattice parameters a = 40.2744 (4), b = 5.0976 (5), c = 27.698 (4) Šand ß = 105.729 (6)°. After dynamical refinement, its absolute structure was determined by comparing the R factors and calculating the z-scores of the two possible enantiomorphs of beauveriolide I.

Preparation and Characterization of Metalloporphyrin Tröger's and Spiro-Tröger's Base Derivatives.

A series of metalloporphyrin dimers as Tröger's bases 1 or spiro-Tröger's bases 2 was prepared starting from five different C4-symmetry porphyrin derivatives substituted in meso-positions by Ph, 3-MeO-Ph, 4-MeO-Ph, 3,4-(MeO)2-Ph, or 3,5-(MeO)2-Ph. Free-base porphyrins were converted to metalloporphyrins, which were subsequently nitrated with nickel(II), copper(II), or zinc(II) nitrate to give ß-nitrometalloporphyrins. These were further reduced to ß-aminometalloporphyrins and treated with a methanal equivalent under acidic conditions to selectively obtain Tröger's base 1, spiro-Tröger's base 2, or a mixture of both, in yields up to 41% of 1 and 45% of 2 depending on the reaction conditions used. The ratio of 1 to 2 was influenced by the methanal equivalent used, the strength of the acid, and, above all, the solvent. The presence of a metal ion within the porphyrin core and the use of a chlorinated solvent were found to be essential for the formation of spiro-Tröger's base 2. The molecular structure of spiroTB 2a-Ni2 was proven by electron diffraction.