Highly Diastereaselective Synthesis of Anti-metabolic Peptide Mimics

利用我国发明的掩膜酰基氰化物（MAC）试剂，研究了钯催化取代的乙烯基氮基苯胺的高区域和立体选择性碳-碳键形成反应。这些反应为二肽模拟物提供了重要的合成中间体，其酰胺键被取代为碳-碳双键。以4-甲苯磺酰基作为氮的保护基团时，成功地进行了选择性碳-碳键形成反应。然而，产物的相对立体化学尚未确定。此外，当使用反式叠氮啶衍生物时，立体选择性较低。用2,4,6-三甲基苯磺酰基代替4-甲苯磺酰基时，反式和顺式叠氮啶的化学收率、区域选择性和立体选择性都得到了极大的提高（>99%）。证实了反式和顺式叠氮嘧啶产物的相对立体化学性质。这一新发现为人工肽的合成提供了有用的技术，并为后蛋白质组学研究提供了前景。

A palladium-catalyzed highly regio- and stereoselective carbon-carbon bond formation reaction of substituted vinyl azilidine was developed using Masked Acyl Cyanide(MAC)reagent, which was previously invented by us. These reactions gave an important synthetic intermediate toward dipeptide-mimics, whose amide bond was displaced to carbon-carbon double bonds. When the 4-toluenesulfonyl group was used for protecting group of nitrogen, the selective carbon-carbon bond formation reactions were succeeded. However, the relative stereochemistry of the products was not identified. Furthermore, the stereoselectivity was low when trans-azilidine derivative was used. When the 2,4,6-trimethylbenzenesulfonyl group was used in stead of 4-toluenesulfonyl group, chemical yields, regioselectivity, and stereoselectivity of the reaction from both trans-and cis-azilidine were extremely improved (>99%).The relative stereochemistry of the product from both trans- and cis-azilidines were confirmed. This new finding is a useful technique for the synthesis of artificial peptides and promising for post-proteomics.