Development of New Organozinc-Copper Complexes and their Application to the Synthesis of Peptide Isosteres

新型有机锌-铜配合物的开发及其在肽等排体合成中的应用

• 批准号: 05671869
• 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 General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671869/
• 关键词: Alkene Isostere; Dipeptide Isostere; Organocopper; gamma, delta-Imino-alpha, beta-enoate; Lithium Chloride; Grignard Reagent; Vinyl Glycine; Organozinc-Copper Complex; アジリジノ-α,β-エノエイト

The following new results have been obtained :1.New organozinc reagents and their Lewis-acid complexes were prepared by reaction of organozinc with Cu (I) slats. It is found that these new reagents were highly effective for the stereo-and regioselective 1,3-chirality transfer reactions of a vinyl group.2.It is found that the above reagents can be prepared from both organolithium and Grignard reagents. Addition of LiCl stabilize the reagents.3.It is found that the reaction of g-mesylor gamma-tosyloxy-alpha, beta-enoates can be transformed into alpha-vinyl-beta, gamma-enoates in a highly regio-and stereoselective manner.4.Methods for potentially useful isomertization of gamma, delta-imino-alpha, beta-enoates by treatment with Pd (Ph_3) _4 at room temperature have been developed.5.Four L-Leu-PSI [ (E) CH=CH ] L-Leu, L-Leu- PSI [ (E) CH=CH ] D-Leu, L-Val-PSI [ (E) CH=CH ] L-Leu, and L-Val-PSI [ (E) CH=CH ] D-Leu isosteres have been synthsized. Incorporation of these dipeptide isosteres into polypeptides can be done in a highly effective manner. These isosteric peptides showed very high bombesin antagonist activity.

1.通过有机锌与铜（I）盐反应，合成了新的有机锌试剂及其路易斯酸配合物。结果表明，这些新试剂对乙烯基的1，3-手性转移反应具有很高的立体选择性和区域选择性。2.发现有机锂和格氏试剂均可合成上述试剂。3.发现g-甲磺酰基或γ-甲苯磺酰氧基-α，β-烯酸酯的反应可以以高度区域选择性和立体选择性的方式转化为α-乙烯基-β，γ-烯酸酯。5. L-Leu-PSI [（E）CH=CH ] L-Leu，L-Leu-PSI [（E）CH =CH ] D-Leu，L-Val-PSI [（E）CH=CH ] L-Leu和L-Val-PSI [（E）CH=CH ] D-Leu电子等排体的大小已被确定。将这些二肽电子等排体掺入多肽中可以以高度有效的方式进行。这些电子等排肽显示出非常高的蛙皮素拮抗剂活性。

项目成果

井深俊郎 他: "Structure‐Activity Relationships of an Anti‐HIV Peptide" Biochem.Biophys.Res.Commun.(印刷中). (1995)

Toshiro Ibuka 等人：“抗 HIV 肽的结构-活性关系”Biochem.Biophys.Res.Commun.（出版中）。

Yukiyasu Chounan, et.al.: "A Chemical Scale for Electron-Transfer Ability of Methylcopper Reagents." J.Chem.Soc., Chem.Commun.2003-2004 (1994)

Yukiyasu Chounan 等人：“甲基铜试剂电子转移能力的化学标度”。

井深俊郎 他: "A Novel Synthetic Route to Diastereomerically Pure(E)‐Alkene Dipeptide Isosteres from β‐Aziridino‐α,β‐enoates by Treatment with Organocopper Reagents" Angew.Chem.Int.Ed.Engl.33. 652-654 (1994)

Toshiro Ibuka 等人：“通过有机铜试剂处理从 β-氮丙啶基-α,β-烯酸酯合成非对映异构纯 (E)-烯烃二肽等排体的新途径” Angew.Chem.Int.Ed.Engl.33。 -654 (1994)

井深俊郎 他: "Aza-Payne Rearrangement of Activated 2-Aziridinemethanols and 2,3-Epoxyamines under Basic Consitions" J.Org.Chem.60(印刷中). (1995)

Toshiro Ibuka 等人：“碱性条件下活化的 2-氮丙啶甲醇和 2,3-环氧胺的 Aza-Payne 重排”J.Org.Chem.60（出版中）。

井深 俊郎: "A Novel Synthetic Route to Diastereomerically Pure(E)-Alkene Dipeptide Isosteres from β-Aziridino-α,β-enoates by Treatment with Organocopper Reagents" Angew.Chem.Int.Ed.Engl.33(印刷中). (1994)

Toshiro Ibuka：“通过有机铜试剂处理从 β-氮杂环丙啶基-α,β-烯酸酯合成非对映体纯 (E)-烯烃二肽等排体的新途径” Angew.Chem.Int.Ed.Engl.33（印刷中）。 (1994)