AbstractA systematic investigation of a series of santalol and epi‐santalol derivatives by means of ab initio and density functional theory (DFT) calculations together with database‐oriented prediction methods leads to a configurational reassignment within this compound class. The DFT calculations as well as the HOSE‐code and neural network‐based predictions allow deriving a general rule set for unambiguous assignment within this compound class. The methyl group in position 2′ serves as an indication for the configuration at this stereocenter allowing easy differentiation between santalol derivatives and their diastereomers belonging to the epi‐santalol series. Copyright © 2009 John Wiley & Sons, Ltd.