Relative stabilities of cholestadienes calculated by molecular mechanics and semi-empirical methods: application to the acid-catalyzed rearrangement reactions of cholesta-3,5-diene

The study of geochemical transformations undergone by 'biological markers' after their incorporation into sediments is an important field of organic g eochemistry. Combined with laboratory simulation experiments, molecular mec hanics calculations have been shown to be very useful to establish the reac tion pathways, and to predict intermediate components and stable reaction e nd products, especially in the case of the acid-catalyzed isomerization rea ctions of steroid and terpenoid hydrocarbons. Many commercially available s oftwares are able to optimize (minimize) the geometries of molecules and co mpute some of their thermodynamical data with either molecular mechanics (M M) or semi-empirical methods of quantum chemistry. In order to verify the r eliability of these methods, we have computed the relative thermodynamic st abilities of a large number of steradiene isomers with MM3 (Tripos Inc.), M M + (HYPERCHEM(TM)) and MM2 (Chem3D, CambridgeSoft Corp.) empirical force f ields, and with AM1 and PM3 (HYPERCHEM(TM)) semi-empirical methods. The cal culation results of thermodynamic stabilities of steradiene isomers are use d to explain the compounds produced by the rearrangement of cholesta-3,5-di ene when treated with p-toluenesulfonic acid in acetic acid at 70 degreesC. The end products, namely the spirosteradienes 7-8, obtained by this treatm ent are the most stable steradiene isomers according to all computational m ethods. The relative thermodynamic stabilities of cholestadienes are also c onsistent with the mechanism postulated for the spirosteradiene formation p roceeding through a pathway including cholestadienes 2-6 as intermediates. (C) 2000 Elsevier Science Ltd. All rights reserved.