【药物名称】
化学结构式(Chemical Structure):
参考文献No.606954
标题:Diastereoselective synthesis, activity and chiral stability of cyclic alkoxyketone inhibitors of cathepsin K
作者:Fenwick, A.E.; Gribble, A.D.; Ife, R.J.; Stevens, N.; Witherington, J.
来源:Bioorg Med Chem Lett 2001,11(2),199
合成路线图解说明:

Asymmetric opening of epoxide (I) with trimethylsilyl azide in the presence of (R,R)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino-chromium as the chiral catalyst (Salen catalyst) provided the (3S,4R)-azido silyl alcohol (II). Removal of the silyl group with camphorsulfonic acid in MeOH and subsequent reduction of the azido moiety of (II) with hydrogen in the presence of Pd/C afforded the amino alcohol (III). Coupling of (III) with the mixed anhydride prepared from N-Cbz-leucine (IV) and isobutyric acid gave amide (V). The N-carbobenzoxy group of (V) was then removed by hydrogenolysis, yielding amine (VI), which was coupled with benzothiophene-2-carbonyl chloride (VII) to furnish the diamide (VIII). The secondary alcohol of (VIII) was finally oxidized to the target ketone using the Dess-Martin reagent in CH2Cl2.

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