Asymmetric Synthesis of 1-Aza-4-deoxypicropodophyllotoxin
Asymmetric Synthesis of 1-Aza-4-deoxypicropodophyllotoxin
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DOI：
10.1055/s-0033-1338414
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发表时间：
2013-06-01
期刊：
影响因子：
2
通讯作者：
De Borggraeve, Wim M.
中科院分区：
文献类型：
--
作者：
Aigret, Benoit M.;Jacobs, Jeroen;De Borggraeve, Wim M.
在天然产物鬼臼毒素的基础上寻找新的易于获得的类似物的过程中，我们合成了1-氮杂-4-脱氧苦鬼臼毒素，具有良好的总收率和良好的对映选择性。该合成是围绕一个直接的不对称Mannich反应，使用D-脯氨酸作为引入手性中心的关键步骤。我们的1-氮杂-4-脱氧鬼臼毒素的合成受到阻碍，通过增加对差向异构化的C2位置的不稳定性。然而，我们确实合成了一种基于开放内酯类似物的新支架。
In our search for new easily accessible analogues based on the natural product podophyllotoxin, we synthesized 1-aza-4-deoxypicropodophyllotoxin in good overall yield and excellent enantioselectivity. The synthesis was centered around a direct asymmetric Mannich reaction using D-proline as the key step for introduction of the chiral centres. Our synthesis of 1-aza-4-deoxypodophyllotoxin was hindered through the increased instability towards epimerization of the C2 position. We did, however, synthesized a new scaffold based on the opened lactone analogue.