Synthesis of trans-anethole oxide and trans-asarone oxide
Carcinogenesis 20(7), 1303-1307 (1999)
Experimental
Dimethyldioxirane solution in acetone was made freshly by an improved conventional method [1]. After the solution was dried with molecular sieves (4 Å, activated powder), it was titrated iodometically with KI and starch. The titrated dimethyldioxirane solution (~0.08 M solution in acetone, 1.2 equiv.) was added to trans-anethole or trans-asarone in dry acetone (1 ml for 1 mmol) at 0°C and the reaction mixture was stirred for 30 min at room temperature. The reaction solution was evaporated under reduced pressure to afford the epoxides. trans-anethole oxide was a colorless oil. The yellow oil of trans-asarone oxide after vacuum application was dissolved in dry hexane and recrystallized at –20°C for a few days to produce a white solid product (mp. 37–40°C). The yields of these oxides were >95%. The oxides were kept at –80°C in dry nitrogen. In this condition trans-anethole oxide was stable for 1 year and trans-asarone oxide was stable for 1 month.
Purity of trans-anethole oxide and trans-asarone oxide
trans-anethole oxide and trans-asarone oxide were found to have very pure NMR spectra with little or no impurity peaks. The yields of oxides from this method were >95%, which are much better than those of Mohan and Whalen [2] and Greca et al. [3] whose methods used m-chloroperoxybenzoic acid to oxidize anethole or asarone and gave yields of 38 and 52%, respectively.
Stability of trans-anethole oxide and trans-asarone oxide
Both of the oxides were stable in acetone or DMSO for 1 h at 0 or 37°C. In aqueous environments, however, the amount of these epoxides declined, presumably because of their hydration to diols. The half-life of trans-anethole oxide was 7.6 min in 0.1 M potassium phosphate buffer (pH 7.4) at 37°C. The presence of 154 mM KCl lowered the half-life to 4.2 min. Trans-asarone oxide showed shorter half-lives; 4.0 min without or 2.4 min with 154 mM KCl.
[1] Ber., 124, 2377
[2] JOC 10, 2663-2669
[3] Phytochemistry 28, 2319-2321