【药物名称】HBJ-10
化学结构式(Chemical Structure):
参考文献No.685327
标题:Orally active, water-soluble antimalarial 3-aryltrioxanes: Short synthesis and preclinical efficacy testing in rodents
作者:Posner, G.H.; Jeon, H.B.; Ploypradith, P.; Paik, I.-H.; Borstnik, K.; Xie, S.; Shapiro, T.A.
来源:J Med Chem 2002,45(18),3824
合成路线图解说明:

Michael addition of acrylonitrile to the enamine resultant from cyclohexanone (I) and pyrrolidine, followed by alkylation with ethyl bromoacetate, leads to the cyano ester (II). Subsequent Wittig reaction of (II) with methoxymethylene triphenylphosphorane affords the enol ether (III). The ester group of (III) is then reduced to alcohol (IV) using L-selectride. Further intramolecular cyclization of (IV) under acidic conditions gives rise to the bicyclic compound (V). Lithiation of p-bromostyrene (VI) with tert-butyllithium, followed by addition to nitrile (V) produces the ketone adduct (VII). Photooxygenation of (VII), followed by cyclization in the presence of trimethylsilyl triflate, furnishes the fused trioxane derivative (VIII). Finally, oxidative cleavage of the vinyl group of (VIII) with potassium permanganate yields the target carboxylic acid.

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