合成路线1

The condensation of indolizine (I) with 4-chloro-4-oxobutyric acid ethyl ester (II) by means of AlCl3 in dichloromethane gives 4-(3-indolizinyl)-4-oxobutyric acid ethyl ester (III), which is reduced with borane in THF to yield 4-(3-indolizinyl)butyric acid ethyl ester (IV). The condensation of (IV) with 4-acetoxybenzoyl chloride (V) by means of AlCl3 in dichloromethane affords the 1-(4-acetoxybenzoyl)indolizine derivative (VI), which is demethylated with NaH in ethanol to provide the corresponding 4-hydroxybenzoyl derivative (VII). The condensation of (VII) with 1(R)-(4-isobutyl)phenyl-1-butanol under Mitsunobu conditions (DEAD, PPh3) gives the corresponding (S)-ether (XI), which is finally hydrolyzed to the target acid by means of NaOH in methanol/THF. The chiral intermediate alcohol (VIII) has been obtained as follows: The condensation of isobutylbenzene (X) with butyryl chloride (XI) by means of AlCl3 in dichloromethane gives the butyrophenone (XII), which is then enantioselectively reduced with (+)-B-chlorodiisopinocampheyl borane [(+)-DIP- chloride] in isopropanol.