Department of Chemistry, G. Ciamician, University of Bologna, Via Selmi 2, 40126, Bologna, Italy.
Amino Acids. 2011 Aug;41(3):575-86. doi: 10.1007/s00726-011-0921-3. Epub 2011 May 4.
The synthesis of unusual cyclic amino acids, that may be envisaged as proline analogs, is an area of great interest for their potential applications as scaffolds for the design of bioactive peptidomimetics or units for the creation of novel foldamers. We have carried out the preparation of cyclic dehydro-β-amino acids starting from allylic carbonates via a two-step allylic amination/ring closing metathesis (RCM) protocol. The introduction of the allylamino moiety has been carried out either without a catalyst, through an S(N)2' reaction, or in the presence of iridium complexes. The backbone of the allylamino intermediates contains two unsaturations, thus suggesting that RCM could be a valuable tool for the preparation of dihydropyrrole scaffolds. A similar reaction has been already reported in the literature for racemic aromatic-substituted substrates, but no examples of enantiopure derivatives bearing aliphatic chains have been reported. The reaction was optimized by testing different Grubbs' catalysts and carbamate nitrogen protecting groups. Moreover, in view of a future application of these dehydro-β-amino acids as central core of peptidomimetics, the malonate chain was also used to protect nitrogen prior to RCM.
合成不寻常的环状氨基酸，这些氨基酸可以被视为脯氨酸类似物，对于它们作为生物活性肽模拟物设计的支架或新型折叠物单元的构建的潜在应用是非常感兴趣的。我们已经通过两步烯丙基胺化/环 closing metathesis (RCM) 方案从烯丙基碳酸酯开始制备环状脱氢-β-氨基酸。烯丙氨基部分的引入要么在没有催化剂的情况下通过 S(N)2' 反应进行，要么在铱配合物的存在下进行。烯丙基中间体的骨架包含两个不饱和键，因此表明 RCM 可能是制备二氢吡咯支架的有价值的工具。类似的反应已经在文献中报道用于外消旋芳香取代的底物，但没有报道过带有脂肪链的对映纯衍生物的例子。通过测试不同的 Grubbs 催化剂和氨基甲酸酯氮保护基对反应进行了优化。此外，鉴于这些脱氢-β-氨基酸将来可能作为肽模拟物的中心核心，在进行 RCM 之前，也使用丙二酸链来保护氮。
