合成路线1

Synthesis of intermediate (XI) of Scheme 25142902e: Racemic 2,4-diaminobutyric acid (I) was esterified in MeOH in the presence of SOCl2. The resulting methyl ester (II) was cyclized using Dowex 2x8-400 resin to give 3-amino-2-pyrrolidinone (III), which was converted to the trifluoroacetamide (IV) using methyl trifluoroacetate in MeOH. The lactam nitrogen of (IV) was then protected with benzyl chloroformate and lithium hexamethyldisilazide yielding (V). Reduction of (V) with NaBH4, followed by treatment with ethanolic H2SO4 provided ethoxypyrrolidine (VI). Ethyl isovalerate (VII) was converted to the silyl enolate (VIII) employing lithium hexamethyldisilazide and silyl triflate. Coupling of (VIII) with ethoxypyrrolidine (VI) in the presence of BF3-Et2O provided (IX). After hydrolysis of the trifluoroacetamide group of (IX) with K2CO3 yielding (X), its cyclization by means of tert-butylmagnesium chloride yielded the pyrrolopyrrolone system. Separation of the required (3aS, 6aR)-isomer (XI) was achieved by chiral HPLC.