萨波廷（一种来自甜果樟的天然产物）的合成及其癌症化学预防活性
Synthesis and cancer chemopreventive activity of zapotin, a natural product from Casimiroa edulis.
作者信息
Maiti Arup, Cuendet Muriel, Kondratyuk Tamara, Croy Vicki L, Pezzuto John M, Cushman Mark
机构信息
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy Purdue University, West Lafayette, Indiana 47907, USA.
出版信息
J Med Chem. 2007 Jan 25;50(2):350-5. doi: 10.1021/jm060915+.
An efficient method has been developed to synthesize zapotin (5,6,2',6'-tetramethoxyflavone), a component of the edible fruit Casimiroa edulis, on a multigram scale. The synthesis utilizes a regioselective C-acylation of a dilithium dianion derived from a substituted o-hydroxyactophenone to afford a beta-diketone intermediate that can be cyclized to zapotin in good overall yield, thus avoiding the inefficient Baker-Venkataraman rearrangement pathway. Zapotin was found to induce both cell differentiation and apoptosis with cultured human promyelocytic leukemia cells (HL-60 cells). In addition, the compound inhibits 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity with human bladder carcinoma cells (T24 cells), and TPA-induced nuclear factor-kappa B (NF-kappaB) activity with human hepatocellular liver carcinoma cells (HepG2 cells). These data suggest that zapotin merits further investigation as a potential cancer chemopreventive agent.
已开发出一种高效方法，可在多克规模上合成扎波亭（5,6,2',6'-四甲氧基黄酮），它是可食用水果埃氏金橘的一种成分。该合成方法利用了由取代的邻羟基苯乙酮衍生的二锂双负离子的区域选择性C-酰化反应，以得到一种β-二酮中间体，该中间体可环化生成扎波亭，总收率良好，从而避免了效率低下的贝克-文卡塔拉曼重排途径。研究发现，扎波亭可诱导培养的人早幼粒细胞白血病细胞（HL-60细胞）发生细胞分化和凋亡。此外，该化合物可抑制人膀胱癌细胞（T24细胞）中12-O-十四酰佛波醇-13-乙酸酯（TPA）诱导的鸟氨酸脱羧酶（ODC）活性，以及人肝癌细胞（HepG2细胞）中TPA诱导的核因子-κB（NF-κB）活性。这些数据表明，扎波亭作为一种潜在的癌症化学预防剂值得进一步研究。
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