Abstract: Computational methods are used to predict the most favorable site of furano sesquiterpenoids (FNTP) towards attack by a water molecule. The energetic of the various complexes are presented as well as their geometries, including Density Functional Theory (DFT) reactivity descriptors such as; Molecular electrostatic potential, Natural Bond Orbital (NBO), Mulliken Electrostatic Charges, Fukui functions HOMO-LUMO gaps data and interactions energies between FNTPs and water acting as simultaneous proton donor and acceptor, predict the reactivity of different basic sites in the following decreasing sequence: CO17> CO14> O19>O13 for FNTP-1 and CO16> O13 for FNTP-2.