An enantioselective synthesis of the key intermediate for triazole antifungal agents; application to the catalytic asymmetric synthesis of efinaconazole (Jublia).
An enantioselective synthesis of the key intermediate for triazole antifungal agents; application to the catalytic asymmetric synthesis of efinaconazole (Jublia).
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DOI：
10.1021/jo500369y
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发表时间：
2014-03
期刊：
影响因子：
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通讯作者：
K. Tamura;N. Kumagai;M. Shibasaki
中科院分区：
文献类型：
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作者：
K. Tamura;N. Kumagai;M. Shibasaki
开发了一条新的合成路线，这是迄今为止报道的最短的合成路线，可以获得合成各种三唑类抗真菌药物的关键中间体。难以捉摸的四取代立体中心是在高级三氮唑类抗真菌药物中通过酮的催化不对称氰硅化反应构建的。随后的转化在两个一锅操作中进行，提高了向中间体的整体合成效率。该合成方法已成功地应用于依非康唑(Jublia)和雷武康唑的高效对映选择性合成。
A new synthetic route, the shortest reported to date, to access a key intermediate for the synthesis of various triazole antifungal agents was developed. The elusive tetrasubstituted stereogenic center that is essential in advanced triazole antifungal agents was constructed via the catalytic asymmetric cyanosilylation of a ketone. The subsequent transformations were performed in two one-pot operations, enhancing the overall synthetic efficiency toward the intermediate. This streamlined synthetic approach was successfully applied to efficient enantioselective syntheses of efinaconazole (Jublia) and ravuconazole.