Abstract
A quantitative treatment of proton spin-lattice relaxation time (T1) and nuclear Overhauser effect (NOE) has been applied to the conformational analysis of two ML-236B (mevastatin) metabolites, 4β, 6α-dihydroxy ML-236B (1) and 3β-hydroxy ML-236B (2) in solution. The T1 values and NOE factors predicted for several candidate conformers were compared with the observed ones.
For 1, the best agreements between observed and calculated values were obtained when the A ring of its octalin moiety was assumed to adopt a chair conformation, and the B ring, a 7β-sofa conformation. In addition it was found that the δ-lactone side chain should be confined to some limited orientations to give calculated values consistent with the observed T1 values and NOEs. Based on the X-ray derived geometry, a similar analysis was done for 2, to check the validity of the method and to characterize the conformation of the δ-lactone side chain in solution. The δ-lactone side chain of 2 was concluded to have the same conformation as in the crystal state.
The applicability of the distance geometry method to calculate the coordinates of small organic molecules was confirmed.
