Branca Mathieu, Gori Didier, Guillot Régis, Alezra Valérie, Kouklovsky Cyrille
Laboratoire de Chimie des Procédés et Substances Naturelles, ICMMO, CNRS UMR 8182, Bât 410, Université Paris-Sud, F-91405 Orsay, France.
J Am Chem Soc. 2008 May 7;130(18):5864-5. doi: 10.1021/ja801165z. Epub 2008 Apr 15.
A new methodology for the asymmetric synthesis of quaternary alpha-substituted amino acids using memory of chirality has been developed. This strategy employs dynamic axial chirality of tertiary aromatic amides to memorize the initial chirality of an alpha-amino acid during the enolization step. Starting from L-valine, an oxazolidin-5-one containing a tertiary aromatic amide was synthesized in one step and then alkylated with various electrophiles with good yield and enantioselectivity (up to 96%). Quaternary products can be obtained enantiomerically pure by recrystallization. One-step deprotection affords enantioenriched (S)-alpha-methyl valine (ee = 94%) or enantiopure (S)-alpha-isopropyl aspartic acid (ee >99%) in only three steps starting from L-valine.
一种利用手性记忆进行季铵化α-取代氨基酸不对称合成的新方法已被开发出来。该策略利用叔芳酰胺的动态轴向手性在烯醇化步骤中记忆α-氨基酸的初始手性。从L-缬氨酸开始，一步合成了含有叔芳酰胺的恶唑烷-5-酮，然后与各种亲电试剂进行烷基化反应，产率和对映选择性良好（高达96%）。季铵化产物可通过重结晶获得对映体纯品。从L-缬氨酸开始，只需三步，一步脱保护即可得到对映体富集的(S)-α-甲基缬氨酸（ee = 94%）或对映体纯的(S)-α-异丙基天冬氨酸（ee >99%）。
