Combined molecular mechanics (MM2) and molecular orbital (AM1) study of reriplanone-a and analogues. Evaluation of biological activity from electronic properties and geometries. Part 2

Abstract

Combined molecular mechanics (MM) and semiempirical molecular orbital (MO) calculations have been applied to periplanone-A (1), the epoxy epimer (2) and a structurally-related analogue (3). Conformational properties of these compounds have been obtained by the use of MM2 with an additional set of force-field parameters in conjunction with an automatic conformation generating program. The global minimum 1A has the same type of ring conformation as that found in periplanone-B (4). The remarkable contrast between 1 and 4 is the presence in 1 of significant amounts of conformers having different ring conformations such as 1B. In both 2 and 3, which are far less biologically active than 1, 1A ring type conformers exist only in low populations. The conformer distribution of 2 obtained by MM2 well explains the highly complex NMR (2D-NOESY) spectrum. The MM-predicted geometries of the stable conformers of 3 show good agreement with that observed in dynamic NMR spectroscopy. When the 1B ring type conformers are taken into account, the accuracy of the previously proposed index for the evaluation of the pheromone activity of analogues, effective frontier parameter EF(^N)(_S)′, is improved.