THE STRUCTURE OF VELUTINOL-A IS (15R,16R,20S)-14,16 6-SECO-14-BETA,17-ALPHA-PREGN-5-ENE-3-BETA,15-DIOL - A COMBINED QUANTITATIVE OVERHAUSEREFFECT AND MOLECULAR MODELING STUDY/

Velutinol A, a potent bradykinin antagonist isolated from the rhizomes of the native Brazilian plant Mandevilla velutina, has been confirmed to have the title structure through the combined use of quantitative H-1-H-1 nuclear Overhauser enhancement (NOE) data and molecular dynami cs/energy minimisation calculations. The NOE data allowed the;unambigu ous selection of the structure from four possible, closely related, is omeric structures. Interproton distances from the NOE data were within 0.5 Angstrom of those calculated from the optimised model structure f or the rigid section of the molecule and within 0.6 Angstrom when the methyl group was considered. Various models were considered for calcul ating the effective distance to a methyl group undergoing internal mol ecular motion. The most successful in reproducing the experimental dat a was the so-called 'pseudo-atom' approach, with a 0.3 Angstrom correc tion applied to the experimental distances, and the more rigorous Rowa n-Woessner approach, which considers the methyl group rotation to be b y +/- 120 degrees jumps between the positions of potential minima. Thr ough the application of field dependent C-13 relaxation time measureme nts the correlation times for overall motion of velutinol A and intern al motion of the C18 methyl group were found to be 0.34 x 10(-10) and 0.05 x 10(-10) s, respectively, The C-13 spin-lattice relaxation of th e sp(3) carbons is dominated by the C-13-H-1 dipole-dipole mechanism, however the relaxation time for the sp(2) carbon C5 is strongly field dependent, and a value of 227 ppm is obtained for the chemical shift a nisotropy.