Practical catalytic enantioselective synthesis of α,α-dialkyl-α-amino acids by chiral phase-transfer catalysis
Practical catalytic enantioselective synthesis of α,α-dialkyl-α-amino acids by chiral phase-transfer catalysis
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DOI：
10.1021/ja0007051
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发表时间：
2000-05-31
影响因子：
15
通讯作者：
Maruoka, K
中科院分区：
文献类型：
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作者：
Ooi, T;Takeuchi, M;Maruoka, K
非蛋白原性 R, R-二烷基-R-氨基酸在具有增强特性的肽的设计中发挥了特殊作用。 1 这不仅是因为它们具有立体化学稳定的季碳中心，还因为它们与肽的结合会对构象偏好产生显着影响，最终为阐明酶促机制提供有用的信息。此外，R, R-二烷基-R-氨基酸本身通常是有效的酶抑制剂3，并且还构成了一系列用于合成各种生物活性化合物的有趣的构建模块。 4 因此，开发真正有效的制备方法，特别是对映体纯的形式，已变得非常重要，并且为此目的进行了大量研究，如最近的优秀评论所示。 5 然而，仅报道了少数催化系统，其普遍适用性有限。 6, 7 在此我们希望公开，使用我们最近推出的C2-对称手性季铵盐3作为催化剂，在相转移催化条件下，通过甘氨酸叔丁酯1的醛亚胺席夫碱的一锅双烷基化，可以以高度对映选择性的方式制备R,R-二烷基-R-氨基酸；因此，图8为从相应的R-氨基酸实际不对称合成R，R-二烷基-R-氨基酸铺平了道路。
Nonproteinogenic R, R-dialkyl-R-amino acids have played a special role in the design of peptides with enhanced properties. 1 This is not only because they possess stereochemically stable quaternary carbon centers but also because their incorporation into peptides results in the significant influence on the conformational preferences, which eventually provides useful information for the elucidation of enzymatic mechanisms. 2 Furthermore, R, R-dialkyl-R-amino acids themselves are often effective enzyme inhibitors3 and also constitute a series of interesting building blocks for the synthesis of various biologically active compounds. 4 Accordingly, development of truly efficient methods for their preparation, especially in an enantiomerically pure form, has become of great importance and numerous studies have been made for this purpose as seen in recent excellent reviews. 5 However, only a few catalytic systems have been reported with limited general applicability. 6, 7 Herein we wish to disclose that R, R-dialkyl-R-amino acids can be prepared in a highly enantioselective manner by the one-pot, double alkylation of aldimine Schiff base of glycine tert-butyl ester 1 under phase-transfer catalytic conditions using our recently introduced C2-symmetric chiral quaternary ammonium salts 3 as catalysts; 8 thus paved the way for practical asymmetric synthesis of R, R-dialkyl-R-amino acids from the corresponding R-amino acids.