Syntheses and pharmacological activities of chiral fomocaines

The syntheses of two chiral fomocaines namely rac ({4-[2-methyl-3-(morpholi n-4-yl)propyl]benzyl}-phenyl-ether(O/G 3) and rac {4-[1-methyl-3-(morpholin -4-yl)propyl]benzyl}-phenyl-ether) (O/G 5) are reported. These compounds ar e part of a new research program concerning the relation between chirality and local anaesthetic activity in the group of fomocaines. The yield over f ive steps is in the range of 9% (O/G 3) up to 19,2% (O/G 5). The racemates were resoluted via the diastereomeric salts formed with (+)- or (-)-campher sulfonic acid. The chromatographic resolution in analytical scale is succes sful using a Daicel OD-column. The enantiomers are stable. The surface anae sthesia of the racemates as well as of the enantiomeres is weaker in compar ison with fomocaine. The rate of tissue irritation is higher. The LD50 (mou se i.v.) is in the range between 290-390 mg/kg, while fomocaine shows a LD5 0 value of 175 mg/kg.