Stereocontrolled synthesis of syn-β-Hydroxy-α-amino acids by direct aldolization of pseudoephenamine glycinamide.
Stereocontrolled synthesis of syn-β-Hydroxy-α-amino acids by direct aldolization of pseudoephenamine glycinamide.
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DOI：
10.1002/anie.201400928
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发表时间：
2014-04-25
影响因子：
16.6
通讯作者：
Myers, Andrew G.
中科院分区：
文献类型：
--
作者：
Seiple, Ian B.;Mercer, Jaron A. M.;Sussman, Robin J.;Zhang, Ziyang;Myers, Andrew G.
β-羟基-α-氨基酸在化学合成中作为手性结构单元发挥着重要作用，是许多重要药物的前体。我们开发并在此报告了一种通过伪苯那明甘氨酰胺醛醇缩合合成 β-羟基-α-氨基酸衍生物的方法，该方法可以通过单瓶方案由伪苯那明制备。在氯化锂存在下，(R,R)-或(S,S)-伪苯那敏甘氨酰胺与六甲基二硅氮基锂发生烯醇化，然后添加醛或酮底物，得到分别与L-或D-苏氨酸立体化学同源的羟醛加成产物。这些产品通常为固体，可以以立体异构纯形式获得，产率为 55-98%，并且很容易通过温和水解转化为 β-羟基-α-氨基酸，或通过硼氢化钠还原转化为 2-氨基-1,3-二醇。这种新的化学物质极大地促进了几种不同类别的新型抗生素的构建。
β-Hydroxy-α-amino acids figure prominently as chiral building blocks in chemical synthesis, serving as precursors to numerous important medicines. We have developed and here report a method for the synthesis of β-hydroxy-α-amino acid derivatives by aldolization of pseudoephenamine glycinamide, which can be prepared from pseudoephenamine in a one-flask protocol. Enolization of (R,R)- or (S,S)-pseudoephenamine glycinamide with lithium hexamethyldisilazide in the presence of lithium chloride followed by addition of an aldehyde or ketone substrate affords aldol addition products that are stereochemically homologous with L- or D-threonine, respectively. These products, which are typically solids, can be obtained in stereoisomerically pure form in yields of 55–98%, and are readily transformed into β-hydroxy-α-amino acids by mild hydrolysis or into 2-amino-1,3-diols by reduction with sodium borohydride. This new chemistry greatly facilitates the construction of novel antibiotics of several different classes.
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影响因子：
15
作者：
BELOKON, YN;ZELTZER, IE;BELIKOV, VM
通讯作者：
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影响因子：
3.6
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影响因子：
2.1
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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