Seven‐Step Synthesis of All‐Nitrogenated Sugar Derivatives Using Sequential Overman Rearrangements
Seven‐Step Synthesis of All‐Nitrogenated Sugar Derivatives Using Sequential Overman Rearrangements
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使用顺序 Overman 重排七步合成全氮化糖衍生物
DOI：
10.1002/anie.202015141
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Chida Noritaka
中科院分区：
文献类型：
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作者：
Okuyama Yuya;Kidena Mayu;Kato Erina;Kawano Sayaka;Ishii Koki;Maie Kenta;Miura Kazuki;Simizu Siro;Sato Takaaki;Chida Noritaka
全氮化糖（ANS），其中碳水化合物中的所有羟基都被氨基取代，预计是具有有用生物活性的特殊结构。然而，由于多氨基的安装困难，ANS 的合成一直具有挑战性。我们在此报告了一种从市售单糖通过七个步骤合成全乙酰化 ANS 的简明合成路线。成功的关键是使用连续的奥弗曼重排，它可以用氨基同时正式取代单糖中的四个或五个羟基。通过仲醇的手性转移，从不同的初始单糖开始，通过相同的反应顺序可以获得各种 ANS。还证明了所得全乙酰化 ANS 的转化，例如糖基化和脱乙酰化。生物学研究表明，ANS 修饰的胆固醇对人类癌细胞系具有细胞毒性，而 ANS 和胆固醇均没有细胞毒性。
All‐nitrogenated sugars (ANSs), in which all hydroxy groups in a carbohydrate are replaced with amino groups, are anticipated to be privileged structures with useful biological activities. However, ANS synthesis has been challenging due to the difficulty in the installation of multi‐amino groups. We report herein the development of a concise synthetic route to peracetylated ANSs in seven steps from commercially available monosaccharides. The key to success is the use of the sequential Overman rearrangement, which enables formal simultaneous substitution of four or five hydroxy groups in monosaccharides with amino groups. A variety of ANSs are available through the same reaction sequence starting from different initial monosaccharides by chirality transfer of secondary alcohols. Transformations of the resulting peracetylated ANSs such as glycosylation and deacetylation are also demonstrated. Biological studies reveal that ANS‐modified cholesterol show cytotoxicity against human cancer cell lines, whereas each ANS and cholesterol have no cytotoxicity.