Biomimetic-type synthesis of benzo[a]naphthacenequinones related to pradimicinone
Biomimetic-type synthesis of benzo[a]naphthacenequinones related to pradimicinone
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DOI：
10.1021/jo9918089
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发表时间：
2000-05-19
影响因子：
3.6
通讯作者：
Hayat, N
中科院分区：
文献类型：
--
作者：
Krohn, K;Bernhard, S;Hayat, N
已知的具有苯并[a]-萘并萘醌骨架的抗生素的数量已经增长到20多种化合物。最简单的代表G-2N和G-2A 1以及马杜拉羟基内酯2的衍生物具有抗菌性能。结构更复杂的O-糖苷普拉米菌素3 -5 [例如，普拉米菌素A（1），方案1]和benanomicins 6 -8显示出显著的体内抗真菌活性。9-14真菌病（例如，由卡氏肺孢子虫引起）是目前免疫缺陷患者治疗中的严重问题，迫切需要新的抗真菌药物。Benanomicins A和B还抑制T细胞感染人类免疫缺陷病毒（HIV）和HIV引起的合胞体形成。普拉米星的抗念珠菌作用至少部分归因于普拉米星A16-18的钙结合以及糖残基与真菌和病毒的细胞表面的特异性结合。生物活性取决于短肽链和5-OH处糖苷糖的存在，如普拉米星A的式所示。最近，Suzuki等人描述了普通普拉米星/贝那霉素苷元的一种巧妙的合成。该合成基于分子内Heck反应以构建AC联芳基键和碘化钐。介导的频哪醇偶联用于在C-5和C-6处引入两个羟基。以前，针对相关的5，6-双脱氧化合物的Diels-Alder方法未能在C-14处引入酚基。二十一、二十二
The number of known antibiotics with the benzo [a]-naphthacenequinone skeleton has grown to more than 20 compounds. The most simple representatives G-2N and G-2A1 and also derivatives of madurahydroxylactone2 have antibacterial properties. The structurally more complex O-glycosidic pradimicins3-5 [eg, pradimicin A (1), Scheme 1] and benanomicins6-8 show remarkable in vivo antifungal activity. 9-14 Mycoses (eg, by Pneumotis carnii) represent severe problems in current therapy of immunodeficient patients, and there is an urgent need for new antimycotic agents. 15 Benanomicins A and B also inhibit infection of T-cells with human immunodeficiency virus (HIV) and syncytium formation by HIV. 11 At least part of the pradimicins’ anticandidal effect is attributed to calcium binding of pradimicin A16-18 and a specific binding of the sugar residues with the cell surface of fungi and viruses. 19 The biological activity depends on the presence of the short peptide chain and the glycosidic sugars at 5-OH as shown in the formula of pradimicin A.Recently, an elegant synthesis of the common pradimicin/benanomicin aglycon was described by Suzuki et al. 20 The synthesis was based on an intramolecular Heck reaction to construct the AC biaryl bond and a samarium iodide-mediated pinacol coupling for the introduction of the two hydroxyl groups at C-5 and C-6. Previously, Diels-Alder approaches aimed at the related 5, 6-dideoxy compounds failed to introduce the phenolic group at C-14. 21, 22