【药物名称】
化学结构式(Chemical Structure):
参考文献No.681691
标题:4-Phenylbutanoyl-2(S)-acylpyrrolidines and 4-phenylbutanoyl-L-prolyl-2(S)-acylpyrrolidines as prolyl oligopeptidase inhibitors
作者:Wall閚, E.A.; Christiaans, J.A.M.; Saario, S.M.; Forsberg, M.M.; Venalainen, J.I.; Paso, H.M.; Mannisto, P.T.; Gynther, J.
来源:Bioorg Med Chem 2002,10(7),2199
合成路线图解说明:

L-Proline (I) is protected as its N-Boc derivative (II) with Boc2O/NaOH in a two-phase system. N-Boc-Proline (II) is further converted into diazo ketone (III) via activation with ethyl chloroformate, followed by condensation with diazomethane. Subsequent treatment of diazo ketone (III) with AcOH leads to the acetoxy ketone (IV). Then, acidic N-Boc group cleavage in (IV) furnishes amine (V). On the other side, L-proline (I) is acylated by 4-phenylbutyryl chloride to produce the corresponding amide (VI). Coupling between 2-(acetoxyacetyl)pyrrolidine (V) and N-(phenylbutyryl)proline (VI) via activation with pivaloyl chloride leads to the amide adduct (VII). Finally, methanolysis of the acetate ester group of (VII) provides the target hydroxyacetyl compound.

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