Stereocontrolled synthesis of methyl silanediol peptide mimics
Stereocontrolled synthesis of methyl silanediol peptide mimics
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DOI：
10.1021/jo701907d
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发表时间：
2007-12-21
影响因子：
3.6
通讯作者：
Skrydstrup, Troels
中科院分区：
文献类型：
--
作者：
Nielsen, Lone;Lindsay, Karl B.;Skrydstrup, Troels
手性亚磺胺与(甲基二苯基硅基)锂反应得到的α-(甲基二苯基硅基)亚磺胺具有很好的非对映选择性，并且产率很高。亚胺上的α-质子的存在也是可以容忍的。亚磺酰胺助剂很容易通过甲醇盐酸处理而被移除，生成的胺相应地延伸到肽链中。二苯基硅基部分是相应硅二醇的弹性保护基团，可以通过TfOH处理，然后水解来揭开它的面孔。粗硅二醇可通过TMSCI保护被分离提纯为其相应的双TMS硅氧烷，并通过KOH水溶液水解转化为所需的硅二醇。描述了将这种方法应用于生物相关的硅烷二醇多肽模拟物以期抑制蛋白酶的努力。
The treatment of chiral sulfinimines with (methyldiphenylsilyl)lithium gives alpha-(methyldiphenylsilyl)sulfinamides with excellent diastereoselectivity, and in good yield. The presence of alpha-protons on the imines is also well tolerated. The sulfinamide auxiliary is easily removed via treatment with methanolic HCl and the resulting amine extended into peptide chains accordingly. The diphenylsilyl moiety is a resilient protecting group for the corresponding silanediol, which can be unmasked via treatment with TfOH, followed by aqueous hydrolysis. The crude silanediol may be isolated and purified as its corresponding bis-TMS siloxane via protection with TMSCI, and converted back to the desired silanediol via hydrolysis with aqueous KOH. Efforts to apply this approach to biologically relevant silanediol peptide mimics, with a view to protease inhibition, are described.