合成路线1

Intermediate (XXXVIII) can be prepared by several alternative methods. Protection of diallylamine (XXXIX) with benzyl chloroformate and Et3N in CH2Cl2 yields the benzyloxycarbonyl derivative (XL), which undergoes ring-closing metathesis in the presence of Grubbs’ catalyst to give 1-Cbz-3-pyrroline (XLI). Reaction of compound (XLI) with NBS in aqueous DMSO followed by treatment of the resulting bromohydrin with 1 N NaOH leads to epoxide (XLII), which undergoes ring opening with NaN3 in aqueous dioxane to afford the racemic trans-azidoalcohol (XLIII). Resolution of rac-(XLIII) is then effected by incubation with lipase PS in the presence of vinyl acetate in i-Pr2O to give the (R,R)-acetate (XLIV) along with unreacted (S,S)-alcohol (XLIII). Methylation of (S,S)-alcohol (XLIII) with iodomethane and NaH affords ether (XLV), which is submitted to azide group reduction by means of PPh3 in THF/H2O to give amine (XLVI). Protection of amine (XLVI) with Boc2O and Et3N followed by selective removal of the Cbz group in the resulting bis-carbamate (XLVII) using poly(methylhydrosiloxane) and Pd/C in EtOH leads to the pyrrolidine (XLVIII), which is finally treated with Boc2O and Et3N .