School of Pharmacy and Department of Chemistry, University of Reading, Whiteknights, Reading, Berks RG6 6AD, UK.
J Am Chem Soc. 2009 Nov 11;131(44):16016-7. doi: 10.1021/ja9070915.
A highly stereoselective synthesis of conformationally constrained cyclic gamma-amino acids has been devised. The key step involves an intramolecular cyclization of a nitronate onto a conjugated ester, promoted by a bifunctional thiourea catalyst. This methodology has been successfully applied to generate a variety of gamma-amino acids, including some containing three contiguous stereocenters, with very high diastereoselectivity and excellent enantioselectivity. It is postulated that an interaction that is key to the success of the process is the simultaneous coordination of the thiourea functionality to both the conjugated ester and the nitronate. Finally, the synthetic utility of these compounds is demonstrated in the synthesis of two dipeptides derived from the C- and N-termini.
已设计出一种高度对映选择性合成构象受限的环状γ-氨基酸的方法。关键步骤包括双功能硫脲催化剂促进的硝酮对共轭酯的分子内环化。该方法已成功应用于生成多种γ-氨基酸，包括一些含有三个连续手性中心的γ-氨基酸，具有非常高的非对映选择性和优异的对映选择性。据推测，对该过程成功至关重要的相互作用是硫脲官能团同时与共轭酯和硝酮配位。最后，这些化合物的合成实用性在两种源自 C 端和 N 端的二肽的合成中得到了证明。
