Transition Metal-catalyzed Isomerization of Aziridines and Its Application to the Synthesis of Highly Active Isosteres

过渡金属催化氮丙啶异构化及其在高活性电子等排体合成中的应用

• 批准号: 08672420
• 负责人: IBUKA Toshiro
• 金额: $ 1.34万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672420/
• 关键词: aziridine; isomerization; transition metal catalyst; alkene isostere; palladium (0)

Transition metal-catalyzed isomerization of aziridines and its application to the synthesis of highly active isosteres has been investigated.1.A thermodynamic relative stabilities between 2,3-cis-3-alkyl-2 vinyl-N-methanesulfonylaziridine and its 2,3-trans-isomers have been investigated by ab initio calculations. It became apparent that 2,3-cis-3-alkyl-2 vinyl-N-methanesulfonylaziridine is more stable than its 2,3-trans-isomer.2.2,3-cis-3-Alkyl-2-vinyl-N-methanesulfonylaziridine is more stable than its 2,3-trans-isomer by ca. 1.0kcal/mol.3.Chiral 2-vinylaziridines bearing an N-aklylsulfonyl or N-arylsulfonyl group were synthesized from either natural alpha-amino acids or chiral 2,3-epoxy alcohols.4.Palladium (0)-catalyzed reactions of 2,3-trans-N-methanesulfonyl-or 2,3-cis-N-(arenesulfonyl)-3-alkyl-2-vinylaziridines gave equilibrium mixtures. Palladium (0)-catalyzed reactions of 2,3-trans-N-methanesulfonylaziridines gave a 95 : 5 equilibrium mixture of 2,3-cis-and 2,3-trans-isomers.5.An efficient synthetic route to (E)-alkene dipeptide isosteres from 2,3-cis-3-alkyl-2-vinylaziridines have been developed.Bioactive peptides involving various (E)-alkene dipeptide isosteres have been synthesized.

本文研究了过渡金属催化的氮丙啶异构化反应及其在高活性电子等排体合成中的应用。1.用从头算方法研究了2，3-顺式-3-烷基-2-乙烯基-N-甲磺酰基氮丙啶及其2，3-反式异构体的热力学相对稳定性。2.2，3-顺式-3-烷基-2-乙烯基-N-甲磺酰基氮丙啶比其2，3-反式异构体更稳定。3.以天然α-氨基酸或手性2，3-环氧醇为原料，合成了带有N-烷基磺酰基或N-芳基磺酰基的手性2-乙烯基氮杂环丙烷。4.钯（0）催化2，3-反式-N-甲磺酰基或2，3-顺式-N-（芳烃磺酰基）-3-烷基-2-乙烯基氮杂环丙烷的反应，得到了平衡混合物。5.以2，3-顺式-3-烷基-2-乙烯基氮杂环丙烷为原料合成了（E）-烯烃二肽电子等排体，合成了含有多种（E）-烯烃二肽电子等排体的生物活性肽。

项目成果

Norio Mimura: "An Unusual Thermodynamic Preference of Chiral N-Arylsulfonyl cis-3-Alkyl-2-vinylaziridines over their trans-Isomers : Palladium (0)-catalyzed Eqyilibration Reaction" J.Chem.Soc., Chem.Commun.351-352 (1996)

Norio Mimura：“手性 N-芳基磺酰基 cis-3-Alkyl-2-vinylaziridines 相对于其反式异构体的异常热力学偏好：钯 (0) 催化的平衡反应”J.Chem.Soc.、Chem.Commun.351-

Kyoko Miyasaka: "Involvement of Cholinergic Process in Cholecystokinin (CCK) Release by Luminal Oleic Acid" J.Autonomic Nervous System. 63. 179-182 (1997)

Kyoko Miyasaka：“胆碱能过程参与管腔油酸释放胆囊收缩素 (CCK)”J.自主神经系统。

Hirokazu Tamamura: "Regiospecific Ring-opening Reactions of Aziridines bearing an alpha, beta-Unsaturated Ester Group with Trifluoroacetic Acid : Application to Stereoselective Synthesis of (E)-Alkene Dipeptide Isosteres" Chem.Commun. 2327-2328 (1997)

Hirokazu Tamamura：“带有 α、β-不饱和酯基的氮丙啶与三氟乙酸的区域特异性开环反应：在 (E)-烯烃二肽等排体的立体选择性合成中的应用”Chem.Commun。

Toshiro Ibuka: "The Aza-Payne Rearrangement : Synthetically Valuable Equilibration" Chem.Soc.Reu. 7(in press). 0000-0000 (1998)

Toshiro Ibuka：“Aza-Payne 重排：具有综合价值的平衡”Chem.Soc.Reu。

Noda Masaki: "A highly Stereoselective Synthesis of the Functionalized(E)-Alkene Dipeptide Isosteres of Trp-Val via Organocyanocopper-Mediated Reaction" Chem.Pharm.Bull.45. 1259-1264 (1997)

Noda Masaki：“通过有机氰铜介导的反应高度立体选择性合成 Trp-Val 的功能化 (E)-烯烃二肽等排体”Chem.Pharm.Bull.45。