Synthesis and biological evaluation of ABCD ring fragments of the kibdelones.
Synthesis and biological evaluation of ABCD ring fragments of the kibdelones.
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DOI：
10.1002/anie.201007613
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发表时间：
2011-03-07
影响因子：
16.6
通讯作者：
Porco, John A., Jr.
中科院分区：
文献类型：
--
作者：
Sloman, David L.;Mitasev, Branko;Scully, Stephen S.;Beutler, John A.;Porco, John A., Jr.
kibdelones A-C（1 - 3）及其同分异构体代谢物（如isoibdelone C； 4）是最近由Capon及其同事从澳大利亚稀有放线菌Kibdelosporangium sp.中分离到的六环四羟基蒽酮天然产物（图1）一个有趣的性质是基苯酮B(2)和C(3)通过酮-烯醇互变异构反应和醌-对苯二酚氧化还原反应，容易平衡成1 - 3的混合物相关的天然产物包括西马霉素α(5)，它已被证明能使癌细胞对包括纳摩尔浓度的博来霉素在内的细胞毒性药物敏感，并表现出有效的抗疟疾和抗球虫活性对kibdelones在NCI人类癌细胞系60细胞组中的评估显示，它们在低纳摩尔浓度下对许多人类肿瘤细胞系有活性。例如，kibdelone A对SR（白血病）肿瘤细胞系的GI50为1.2 nm，对SN12C（肾）细胞癌的GI50 < 1 nm此外，kibdelones显示出新的肿瘤细胞生长抑制比较分析谱。目前已经有大量的工作用于合成多环口山酮类，包括cervinomycin A2(6)，但对相应的四羟基山酮类的合成研究比较有限我们最初构建ABCD环片段7的策略是杂环醌8和羟基苯乙烯9的Diels-Alder环加成（方案1）。
The kibdelones A–C (1–3) and their isomeric metabolites (cf. isokibdelone C; 4) are hexacyclic tetrahydroxanthone natural products recently isolated by Capon and co-workers from the rare Australian actinomycete Kibdelosporangium sp.(Figure 1).[1] An interesting property is the facile equilibration of kibdelones B (2) and C (3) to a mixture of 1–3 through keto–enol tautomerizations followed by quinone–hydroquinone redox reactions.[1] Related natural products include simaomicin α (5) which has been shown to sensitize cancer cells to cytotoxic agents including bleomycin at nanomolar concentrations and to exhibit potent antimalarial and anticoccidial activities.[2] Evaluation of the kibdelones in the NCI 60-cell panel of human cancer cell lines revealed that they are active at low nanomolar concentrations against a number of human tumor cell lines. For example, kibdelone A has a GI50 of 1.2 nm against a SR (leukemia) tumor cell line and< 1 nm (GI50) against SN12C (renal) cell carcinoma.[1] In addition, the kibdelones were shown to display novel COMPARE analysis profiles for cancer cell growth inhibition. There has been substantial work towards the synthesis of the polycyclic xanthones including cervinomycin A2 (6), but more limited studies on the synthesis of the corresponding tetrahydroxanthones.[3] Our initial strategy to construct the ABCD ring fragment 7 involved Diels–Alder cycloaddition of heterocyclic quinone 8 and hydroxystyrene 9 (Scheme 1).
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影响因子：
15
作者：
FISHER, MJ;HEHRE, WJ;OVERMAN, LE
通讯作者：
OVERMAN, LE
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Junicke, H;Bruhn, C;Steinborn, D
通讯作者：
Steinborn, D