合成路线1

The reaction of succinic anhydride (I) with the lithium salt of the chiral oxazolidinone (II) in THF gives 3-(hydroxysucccinyl)-4(S)-isopropyloxazolidin-2-one (III), which is treated successively with oxalyl chloride, CH2N2 and HBr to yield the bromomethyl derivative (IV). The cyclization of (IV) with thiourea in refluxing isopropanol affords the 2-aminothiazol derivative (V), which is protected with 2,2,2-trichloroethyl chloroformate by means of DIEA and DMAP in dichloromethane giving the carbamate (VI). The reaction of (VI) with tert-butyl 2-bromoacetate (VII) by means of sodium hexamethyldisilazane (NaHMDS) in THF yields the chiral butyrate (VIII), which is hydrolyzed with TFA in dichloromethane to the chiral butyric acid (IX). The condensation of (IX) with the intermediate amine (X) by means of BOP-PF6 and DIEA in DMF affords the corresponding amide (XI), which is treated with magnesium methoxide in methanol to eliminate the oxazolidinone group (the chiral inductor) providing the methyl ester (XII). The hydrolysis of (XII) with NaOH, followed by condensation with amine (XIII) (J Org Chem 1988, 53: 6109; J Med Chem 1993, 36: 449) gives the protected intermediate (XIV), which is finally deprotected by reaction with Zn/HCl in aqueous dioxane.