Practical synthesis of enantiomerically pure β2-amino acids via proline-catalyzed diastereoselective aminomethylation of aldehydes
Practical synthesis of enantiomerically pure β2-amino acids via proline-catalyzed diastereoselective aminomethylation of aldehydes
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DOI：
10.1021/ja070063i
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发表时间：
2007-05-09
影响因子：
15
通讯作者：
Gellman, Samuel H.
中科院分区：
文献类型：
--
作者：
Chi, Yonggui;English, Emily P.;Gellman, Samuel H.
脯氨酸催化的非对映选择性氨甲基化的醛使用手性亚胺离子，从一个容易制备的前体，提供α-取代的-β-氨基醛与85：15至90：10 dr。α-取代的-β-氨基醛可以被还原为β-取代的-γ-氨基醇，其主要的非对映异构体可以通过结晶或柱色谱分离。氨基醇被有效地转化为受保护的β（2）-氨基酸，其是β-肽、天然产物和其他感兴趣的分子的有价值的构建块。由于氨甲基化和随后反应的条件温和，因此可以用这种方法制备侧链中具有被保护官能团的β（2）-氨基酸衍生物，例如β（2）-高谷氨酸、β（2）-高酪氨酸和β（2）-高赖氨酸。合成路线短，纯化简单;因此，该方法能够以有用的量制备受保护的β（2）-氨基酸。
Proline-catalyzed diastereoselective aminomethylation of aldehydes using a chiral iminium ion, generated from a readily prepared precursor, provides alpha-substituted-beta-amino aldehydes with 85:15 to 90:10 dr. The alpha-substituted-beta-amino aldehydes can be reduced to beta-substituted-gamma-amino alcohols, the major diastereomer of which can be isolated via crystallization or column chromatography. The amino alcohols are efficiently transformed to protected beta(2)-amino acids, which are valuable building blocks for beta-peptides, natural products, and other interesting molecules. Because conditions for the aminomethylation and subsequent reactions are mild, beta(2)-amino acid derivatives with protected functional groups in the side chain, such as beta(2)-homoglutamic acid, beta(2)-homotyrosine, and beta(2)-homolysine, can be prepared in this way. The synthetic route is short, and purifications are simple; therefore, this method enables the preparation of protected beta(2)-amino acids in useful quantities.