Aplyronine A, a Potent Antitumor Substance of Marine Origin, Aplyronines B and C, and Artificial Analogues: Total Synthesis and Structure−Cytotoxicity Relationships
Aplyronine A, a Potent Antitumor Substance of Marine Origin, Aplyronines B and C, and Artificial Analogues: Total Synthesis and Structure−Cytotoxicity Relationships
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Aplyronine A，一种海洋来源的有效抗肿瘤物质，Aplyronine B 和 C，以及人工类似物：全合成和结构-细胞毒性关系
DOI：
10.1021/jo9606113
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发表时间：
1996
影响因子：
3.6
通讯作者：
Kiyoyuki Yamada
中科院分区：
文献类型：
--
作者：
H. Kigoshi;K. Suenaga;Tsuyoshi Mutou;T. Ishigaki;Toshiyuki Atsumi;H. Ishiwata;A. Sakakura;T. Ogawa;M. Ojika;Kiyoyuki Yamada
aplyronine A (1) 是一种有效的海洋来源抗肿瘤物质，通过聚合方法实现了对映选择性全合成。使用 Evans 羟醛反应和 Sharpless 环氧化作为关键步骤，制备了三个片段 4、5 和 6，分别对应 aplyronine A (1) 的 C5−C11、C21−C27 和 C28−C34 部分。 4与碘化物7的偶联反应，随后与砜8的Julia烯化得到C5−C20链段9，而链段5和6之间的Julia偶联反应提供了C21−C34链段10。链段9和10之间的Julia烯化以及随后的四碳同系化反应产生seco酸83，随后通过山口内酯化将其转化为aplyronine A (1)通过引入两种氨基酸。使用[(3,4-二甲氧基苄基)氧基]甲基作为C29处羟基的保护基对于该合成至关重要。还进行了两种天然同源物 aplyronines B (2) 和 C (3) 的对映选择性合成......
The enantioselective total synthesis of aplyronine A (1), a potent antitumor substance of marine origin, was achieved by a convergent approach. Three segments 4, 5, and 6, corresponding to the C5−C11, C21−C27, and C28−C34 portions of aplyronine A (1), were prepared using the Evans aldol reaction and the Sharpless epoxidation as key steps. The coupling reaction of 4 with iodide 7 followed by Julia olefination with sulfone 8 gave the C5−C20 segment 9, while the Julia coupling reaction between segments 5 and 6 provided the C21−C34 segment 10. Julia olefination between segments 9 and 10 and the subsequent four-carbon homologation reaction led to seco acid 83, which was converted into aplyronine A (1) by Yamaguchi lactonization followed by the introduction of two amino acids. The use of the [(3,4-dimethoxybenzyl)oxy]methyl group as a protecting group for the hydroxyl at C29 was crucial for this synthesis. The enantioselective synthesis of two natural congeners, aplyronines B (2) and C (3), was also carried out...