MM3(92) Analysis of Inositol Ring Puckering

Abstract

The molecular mechanics method MM3(92) was used to study the puckering of the nine inositol isomers. Energy surfaces were generated based on the Cremer-Pople puckering definitions and the geometric plate carree representations of Pickett and Strauss. Chair forms are favoured for all the inositol isomers in agreement with experiment. The lowest energy non-chair form, more than 10 kJ/mol in free energy above the chair, is a skew of muco-inositol , in which all the hydroxyls are oriented either equatorially or pseudo-equatorially. Hydrogen-hydrogen coupling constants are in good agreement with experiment. The predicted order of stability for the isomers is scyllo - > myo - > chiro - > neo- >   epi -> muco - ≈ allo -> cis-inositol. This order generally agrees with Angyal's proposed stability order based on the number and type of gauche and 1,3-diaxial ring substituents. In contrast with recent ab initio calculations and values calculated with Angyal's method, the MM3   gas-phase free energy of scyllo-inositol was lower than that of myo-inositol by 5.5 kJ/mol. The calculated transition energy for the chair-to-chair conversion of cis-inositol differs by 12.5-17.2 kJ/mol from the experimental value, depending on the strength of the electrostatic field.