Synthesis of a chiral auxiliary derivative of carvone and its use for the dynamic kinetic resolution of ibuprofen

Introduction Ibuprofen is a non-steroidal anti-inflammatory drug (NSAI) from the family of the arylpropionic acids (Lombardino, 1985). Despite ibuprofen continues to be marketed as racemate, it has been demonstrated that only the (S)enantiomer is responsible for the desired therapeutic effects (Adams et al., 1976). (R)Enantiomer shows some risk of toxicity due to be stored into adipose tissue as glyceryl ester, whose long-term effects are currently unknown (Williams et al., 1986). So far there have been numerous attempts aimed to prepare ibuprofen as an optically pure form, including the resolution of diasteroisomeric salts, the resolution by bioconversion, and asymmetric synthesis using chiral auxiliaries as well as chiral catalysts (Harrison et al., 1970; Larsen et al., 1989; Senanayake et al., 1992). In this paper our findings referred to the synthesis of the chiral auxiliary (-)-1 derived from S-(-)-carvone, and the preliminary results of its use as agent for kinetic dynamic resolution of ibuprofen [(±)-2] (Fig. 1) are reported.