Joseph Foricher

Practical synthesis of (S)-2-(4-fluorophenyl)-3-methylbutanoic acid, key building block for the calcium antagonist Mibefradil

Abstract A short, technically feasible route was developed for the synthesis of (S)2-(4-fluorophenyl)-3-methylbutanoic acid (S)- 2 with an overall yield of 80% starting from 4-fluorophenylacetic acid. Asymmetric hydrogenation of the easily accessible unsaturated acid 3 in the presence of ruthenium(II) carboxylato complexes containing chiral atropisomeric diphosphines afforded (S)- 2 in up to 94% ee. The ee of (S)- 2 was upgraded to 98% by crystallization of its sodium salt. The same protocol was also applied to the synthesis of (S)-2-(4-chlorophenyl)-3-methylbutanoic acid.

Asymmetric enzymatic hydrolysis of prochiral 2-O-allylglycerol ester derivatives

Abstract The generation of optically active glycerol derivatives via enzymatic ester hydrolysis of prochiral 1,3-diacyl derivatives of 2-O-allyl protected glycerol has been investigated. Lipase M-AP, under optimum conditions, afforded asymmetric inductions of 94–96 % ee. The obtained (R)-monoacyl derivative was converted to (S)-configurated tosylglycerol compounds.