Total Synthesis of Chalaniline B: An Antibiotic Aminoxanthone from Vorinostat-Treated Fungus Chalara sp. 6661
Total Synthesis of Chalaniline B: An Antibiotic Aminoxanthone from Vorinostat-Treated Fungus Chalara sp. 6661
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DOI：
10.1021/acs.joc.1c00528
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发表时间：
2021-05-17
影响因子：
3.6
通讯作者：
Blakemore, Paul R.
中科院分区：
文献类型：
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作者：
Khoshbakht, Mahsa;Thanaussavadate, Bongkotrat;Blakemore, Paul R.
Chalaniline B [1-苯胺基-2，8-二羟基-3-（羟甲基）氧杂蒽酮]，一种先前从伏立诺他处理的Chalara种分离的抗生素，由2-羟基咕吨酮经7步制备，该路线包括区域选择性氧化转化（在C1/C3处溴化，酮导向的Pd（II）催化的在C8处羟基化），通过由1，3-二溴-2，8-二甲氧基咕吨酮进行的区域选择性Buchwald-Hartwig胺化反应安装C1-苯胺基部分，以及使用Stille交叉偶联在C3处进行后期羟甲基化。脱羟甲基查拉苯胺B（1-苯胺基-2，8-二羟基吨酮）的生物学评价显示，对两种耐甲氧西林沙门氏菌的MIC值为8 μ g mL（-1）（25 μ M）。aureus和B. B.枯草芽孢杆菌
Chalaniline B [1-anilino-2,8-dihydroxy-3-(hydroxymethyl)xanthone], an antibiotic previously isolated from vorinostat-treated Chalara sp., was prepared in 7 steps from 2-hydroxyxanthone by a route incorporating regioselective oxidative transformations (bromination at C1/C3, ketone directed Pd(II)catalyzed hydroxylation at C8), installation of the C1-anilino moiety by a regioselective Buchwald-Hartwig amination reaction from 1,3-dibromo-2,8-dimethoxyxanthone, and late-stage hydroxymethylation at C3 using a Stille cross-coupling. Biological evaluation of deshydroxymethylchalaniline B (1-anilino-2,8-dihydroxyxanthone) revealed MIC values of 8 mu g mL(-1) (25 mu M) against both methicillin resistant S. aureus and B. subtilis.