Distribution of piperitone oxide stereoisomers in Mentha and Micromeria species and their chemical syntheses

Chiral GC–MS analyses of natural and synthetic trans‐ and cis‐piperitone oxide were performed on an Rt‐βDEX‐sm capillary column in order to clarify the stereochemistry of their enantiomeric forms. Only enantiomerically pure laevo‐rotatory piperitone oxides, (1S,2S,4S)‐trans‐piperitone oxide and (1S,2S,4R)‐cis‐piperitone oxide, were detected by chiral analyses of Micromeria fruticosa (L.) Druce and Mentha longifolia L. The occurrence of the cis‐ and trans‐piperitone oxides was dependent on the population of the species. In all cases (1S,2S,4S)‐trans‐piperitone oxide was detected together with (4S)‐piperitone, while (1S,2S,4R)‐cis‐piperitone oxide was detected together with (4R)‐piperitone in the plants analysed. The four stereoisomers of trans‐ and cis‐piperitone oxide were obtained by alkaline epoxidation of both (4R)‐ and (4S)‐piperitone. The formation of the 1,2‐epoxide can take place on either side of the 1,4‐substituted six‐membered ring. Racemization at C4 was observed under alkaline epoxidation reaction conditions due to keto‐enol tautomerism.