Highly Diastereaselective Synthesis of Anti-metabolic Peptide Mimics

抗代谢肽模拟物的高度非对映选择性合成

• 批准号: 18550094
• 负责人: NEMOTO Hisao
• 金额: $ 2.64万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18550094/
• 关键词: acyl anion equivalents; acyl cyanide; peptide mimics; palladium-catalyzed reaction; azilidine; π-allvlpalladium complex; anti-metabolic; π-アリルパラジウム中う間体

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.

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。

项目成果

Synthesis of Branched Heptaglycerol Bearing Eight Hydroxyl Groups with Four Cyclic Protecting Groups

带有八个羟基和四个环状保护基团的支化七甘油的合成

• 发表时间: 2007
• 期刊: Synlett
• 影响因子: 2
• 作者: Nemoto;Hisao
• 通讯作者: Hisao

Synthesis of alpha-Amino Acid Precursors Directly from Aldehydes using Masked Acyl Cyanide Reagents and N,O-Dialkylated Hydroxylamines,.,2006,71,6038-6043:Journal

使用掩蔽酰氰试剂和 N,O-二烷基化羟胺直接从醛合成 α-氨基酸前体，.,2006,71,6038-6043:Journal

• 发表时间: 2006
• 期刊: J.Org.Chem. 71巻・16号
• 作者: Nemoto;Hisao;Ma;Rijian;Kawamura;Tomoyuki;Kamiya;Masaki;Shibuya;Masayuki
• 通讯作者: Masayuki

Modification of protein with BGL06, a novel branched oligoglycerol derivative

用 BGL06（一种新型支链低聚甘油衍生物）对蛋白质进行修饰

• 发表时间: 2008
• 期刊: BioChim. Biophys. Acta. 1780
• 作者: Yamaguchi;Hiroyuki
• 通讯作者: Hiroyuki

パラジウム触媒を用いたMAC反応剤による多置換ビニルアジリジンの位置及び立体選択的開環反応

使用钯催化 MAC 试剂进行多取代乙烯基氮丙啶的区域选择性和立体选择性开环反应

• 发表时间: 2008
• 作者: Suzuki;Ichiro;Takahashi;Mayuko;Shigenaga;Akira;Nemoto;Hisao;Takeda;Kei;河村知志
• 通讯作者: 河村知志

Modification of protein with BGLO6,a novel branched oligoglycerol derivative

新型支化低聚甘油衍生物BGLO6对蛋白质的修饰

• 发表时间: 2008
• 期刊: Biochim. Biophys. Acta
• 作者: Yamaguchi;Hiroyuki
• 通讯作者: Hiroyuki