Trimethylamine → (-)-Carnitine

Participants

Reaction Steps

The first reaction step is a ring-opening reaction of (S)-3-activated hydroxybutyrolactone expressed by formula 2. The ring-opening reaction of this invention is similar to the reaction in which the ester group is hydrolyzed. However, in view of the reaction mechanism, the general hydrolysis method cannot work due to the presence of the 3-activated hydroxy group which is easily detachable at the β-position of the carbonyl group of the compound of formula 2. In this regard, several commonly known hydrolysis methods have been implemented, but the ring-opening reaction did not occurred with respect to the compound of formula 2. Therefore, the target compound of formula 3 under this invention could be not be obtained. For example, the hydrolysis of the esters using water as a solvent in the presence of sodium hydroxide is known to be irreversible and quantitative. However, when the ring-opening reaction of 3-methanesulfonylhydroxybutyrolactone was attempted among the compounds of formula 2, the compounds without the sulfonylhydroxy group (—OR) were mainly obtained. In addition to sodium hydroxide, various types of bases (e.g., inorganic bases such as potassium hydroxide, or organic amines such as triethylamine and pyridine) have been used in order to carry out the ring-opening reaction. However, the compounds without the sulfonylhydroxy group (—OR) were obtained as main products instead of the target compound of this invention. In particular, based on the U.S. Pat. No. 5,473,104 (1995), (S)-3-methanesulfonyl hydroxybutyrolactone of 1 equivalent and 25% trimethylamine solution of 1˜2 equivalent as a base were mixed. Then, the mixture was stirred and reacted at room temperature. However, the ring-opening reaction was not implemented, and within 10 minutes, it was confirmed by nuclear magnetic resonance analysis that furanone without the methanesulfonyl group was formed in 70˜100% yield. Therefore, L-carnitine could not be formed under the above reaction conditions.

Provenance & Evidence