Total synthesis of 34-hydroxyasimicin and its photoactive derivative for affinity labeling of the mitochondrial complex I
Total synthesis of 34-hydroxyasimicin and its photoactive derivative for affinity labeling of the mitochondrial complex I
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DOI：
10.1002/chem.200305557
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发表时间：
2004-05-03
影响因子：
4.3
通讯作者：
Sinha, SC
中科院分区：
文献类型：
--
作者：
Han, HN;Sinha, MK;Sinha, SC
采用聚合合成策略，实现了34-羟基asiimicin及其3-（4-苯甲酰苯基）丙酸酯的不对称全合成。该酯含有8个不对称中心，是第一个从菊科植物乙酰原中提取的光亲和标记剂。合成过程中的关键转化包括Sharpless不对称二羟基化反应、Wittig烯烃化反应、氧化铼（VII）环化反应、Williamson醚化反应和钯催化的交叉偶联反应。利用靶分子进行牛线粒体nadh -泛醌氧化还原酶（复合体1）的光亲和标记研究，可能有助于揭示这种复杂酶的结构/功能，以及牛油科乙酰原素表现出的高抗肿瘤活性的起源。
The asymmetric total synthesis of the 34-hydroxyasimicin and its 3-(4-benzoylphenyl)propionate ester was achieved by means of a convergent synthetic strategy. This ester, which contains eight asymmetric centers, represents the first photoaffinity-labeling agent that is derived from an Annonaceous acetogenin. The key transformations in the synthesis include the Sharpless asymmetric dihydroxylation reaction, the Wittig olefination reaction, an oxidative cyclization reaction with rhenium(VII) oxide, the Williamson etherification reaction, and a palla-dium-catalyzed cross-coupling reaction. Use of the target molecule for photoaffinity-labeling studies of bovine mitochondrial NADH-ubiquinone oxidoreductase (Complex 1) may shed light on the structure/function of this intricate enzyme and on the origin of the high antitumor activity exhibited by the Annonaceous acetogenins.