Total synthesis of the hydroxyketone kurasoin A using asymmetric phase-transfer alkylation
Total synthesis of the hydroxyketone kurasoin A using asymmetric phase-transfer alkylation
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DOI：
10.1021/jo061395t
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发表时间：
2006-10-27
影响因子：
3.6
通讯作者：
Bedke, D. Karl
中科院分区：
文献类型：
--
作者：
Andrus, Merritt B.;Hicken, Erik J.;Bedke, D. Karl
采用一种新的不对称相转移催化乙醇酸烷基化反应，实现了法尼基转移酶抑制剂kurasoin A的全合成。2,5-二甲氧基苯乙酮7与金银啶催化剂9 （10 mol %）和氢氧化物碱与戊酰苄基溴8的s -烷基化产物10收率高（80-99%），对映选择性好。Baeyer-Villiger氧化，Weinreb酰胺形成，并在es -ether 17上添加苄基Grignard，得到了受保护的靶标。氢氧化锂和过氧化氢生成kurasoin A （[α](D) + 8.4度），没有异构化。
The total synthesis of the farnesyltransferase inhibitor kurasoin A has been achieved using a novel asymmetric phase-transfer-catalyzed glycolate alkylation reaction. 2,5-Dimethoxyacetophenone 7 with cinchonidinium catalyst 9 (10 mol %) and hydroxide base with pivaloyl benzyl bromide 8 provided S-alkylation product 10 in high yield (80-99%) and excellent enantioselectivity. Baeyer-Villiger oxidation, Weinreb amide formation, and benzyl Grignard addition to the TES-ether 17 gave the protected target. Lithium hydroxide and peroxide generated kurasoin A ([alpha](D) + 8.4 degrees) without isomerization.