Importance of sulfoxidation in rapid racemisation of glitazones

AM1 calculations on equilibrium and transition state geometries of keto and enol forms of glitazones were carried out and compared with those of some carbonyl compounds. The results show that the energy requirements for enolisation of glitazones are much higher than the standard carbonyl systems. Neither the ring system, nor the additional functional groups in thiazolidinedione terminal ring facilitate the keto-enol tautomerisation, hence keto-enol tautomerisation cannot be considered as the cause for rapid racemisation in glitazones. Thio compounds are known to undergo reversible oxidation and the barrier for 1, 3-H shift in S-oxide form of thiazolidinediones is significantly lower than all the other agents studied. This study strongly indicates the involvement of S-oxidation in the enhanced rate of racemisation of thiazolidinediones.