Total syntheses of (+)-alopecuridine, (+)-sieboldine A, and (-)-lycojapodine A.
Total syntheses of (+)-alopecuridine, (+)-sieboldine A, and (-)-lycojapodine A.
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DOI：
10.1021/jo301545y
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发表时间：
2012-09
期刊：
影响因子：
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通讯作者：
Xiao‐Ming Zhang;H. Shao;Y. Tu;Fu‐Min Zhang;Shao-Hua Wang
中科院分区：
文献类型：
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作者：
Xiao‐Ming Zhang;H. Shao;Y. Tu;Fu‐Min Zhang;Shao-Hua Wang
(+)-苦杏仁苷、(+)-西波尔丁A和(-)-狼毒碱甲是三种结构独特且相关的石蒜生物碱，通过一种有效的策略以对映体形式合成。(+)-氨基尿苷的主要合成方法是通过羟基环氧化物的半频呐醇重排反应构建具有全碳四元中心的螺环6，9-氮杂碳环，并通过后期SMI(2)介导的分子内偶联反应形成5元环。随后，经过对氧化方法的广泛探索，通过两种不同的生物激励氧化反应，成功地完成了(+)-西博尔丁A和(-)-天冬氨酸A的仿生合成。因此，(+)-西博尔定A通过N-氧化/硝酮形成过程得到(+)-对乙酰尿苷，(-)-糖苷A通过有趣的环半酮形成/氧化二醇裂解途径得到(-)-糖苷A。这些结果证实了三种生物碱之间的生物发生关系。
(+)-Alopecuridine, (+)-sieboldine A, and (-)-lycojapodine A, three structurally unique and related lycopodium alkaloids, have been synthesized in enantiomeric forms through an efficient strategy. The main synthetic approach for (+)-alopecuridine features a semipinacol rearrangement of hydroxyl epoxide to construct the spiro 6,9-azacarbocycles with an all-carbon quaternary center and a late-stage SmI(2)-mediated intramolecular coupling to form the 5-membered ring. Subsequently, the biomimetic synthesis of (+)-sieboldine A and (-)-lycojapodine A was accomplished successfully through two different bioinspired oxidations after a wide search for the oxidation methods. As a result, (+)-sieboldine A was derived from (+)-alopecuridine through an N-oxidation/nitrone formation process and (-)-lycojapodine A through an interesting cyclic hemiketal formation/oxidative diol cleavage pathway. These results confirmed the biogenetic relationship among the three alkaloids.