Total synthesis and structural revision of (+)-amphidinolide W
Total synthesis and structural revision of (+)-amphidinolide W
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DOI：
10.1021/ja049754u
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发表时间：
2004-03-31
影响因子：
15
通讯作者：
Gong, G
中科院分区：
文献类型：
--
作者：
Ghosh, AK;Gong, G
描述了两萜内酯W(2)的对映选择性首次全合成及其C6绝对立体化学(1)的修正。Amphidinolide W(1)，从mamphidiniumsp .中分离得到的12元环内酯类化合物。对多种NCI肿瘤细胞系显示出有效的抗肿瘤特性。该合成具有收敛性，5个手性中心中有4个是通过不对称合成得到的。该合成具有Sharpless不对称二羟基化，非对映选择性烷基化，功能化底物的高效交叉复合，以及使用选择性脂肪酶催化水解初级乙酸基的新型官能团转化。特别值得注意的是，两萜内酯W(1)的C6绝对立体化学现在已经通过我们目前的合成进行了修订。
An enantioselective first total syntheis of amphidinolide W (2) and a revision of its C6 absolute stereochemistry (1) are described. Amphidinolide W (1), a 12-membered macrolide isolated fromAmphidiniumsp., has shown potent antitumor properties against a variety of NCI tumor cell lines. The synthesis is convergent, and four of the five chiral centers were derived through asymmetric synthesis. The synthesis features Sharpless asymmetric dihydroxylation, diastereoselective alkylation, efficient cross metathesis of functionalized substrates, and novel functional group transformations using selective lipase-catalyzed hydrolysis of the primary acetate group. Of particular note, the C6 absolute stereochemistry of amphidinolide W (1) has now been revised through our current synthesis.