Design and synthesis of foldamer, and its application to asymmetric reactions

折叠体的设计合成及其在不对称反应中的应用

• 批准号: 15590011
• 负责人: TANAKA Masakazu
• 金额: $ 2.3万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590011/
• 关键词: disubstituted amino acid; helix; conformation; peptide; chiral center; foldamer; α、α-ジ置換アミノ酸; 不斉炭素; アミノ酸; 2次構造; α,α-ジ置換アミノ酸; クルティウス反応; リパーゼ; 光学分割

Two kinds of optically active cyclic α,α-disubstituted α-amino acids were designed. One is a disubstituted amino acid having a cyclopentane ring (A_<C_5C>^<dOM>), and the other is a disubstituted amino acid having a piperidine skeleton (Pip). Both cyclic disubstituted amino acids have similar characteristics in that the α-carbon atom is not an asymmetric center but chiral centers exist on the cyclic side chain of the amino acids. The A_<C_5C>^<dOM> was synthesized starting from dimethyl L-tartrate as a chiral source, and the Pips were synthesized starting from dimethyl malonate and chiral amines.As a peptide-foldamer, homo- and hetero-peptides containing A_<C_5C>^<dOM> and Pip were prepared by the solution phase method The secondary structures of oligopeptides were studied in solution (in water and TFE solution) and in the solid state. It has become clear that the (S,S)-A_<C_5C>^<dOM> homopeptides having side-chain chiral centers, which do not have an asymmetric center at the α-position, form left-handed 3_<10-> and α-helices both in solution and in the solid state. It should be noted that usually short oligopeptides prepared from normal L-amino acids do not form a stable secondary structure, but short oligopeptides prepared from A_<C_5C>^<dOM> and Pip form one-handed helices. Thus, these results might be valuable for the development of asymmetric reactions using foldamers.

设计了两种具有光学活性的环α，α-二取代α-氨基酸。一种是含环戊环的二取代氨基酸(A_&lt；C_5C&gt；^&lt；Dom&gt；)；另一种是具有哌啶骨架的二取代氨基酸(Pip)。两种环状二取代氨基酸具有相似的特征，即α-碳原子不是不对称中心，但在氨基酸的环状侧链上存在手性中心。以酒石酸二甲酯为手性源合成了A&lt；C5C&gt；^&lt；DOM&gt；，以丙二酸二甲酯和手性胺为原料合成了PIPs，并用溶液相法合成了含有A&lt；C5C&gt；^&lt；DOM&gt；和Pip的同源和杂多肽。显然，具有侧链手性中心的(S，S)-A_&lt；C_5C&gt；^&lt；DOM&gt；同肽在α位置上没有不对称中心，在溶液和固体中都形成左旋3_&lt；10-gt；和α-螺旋。需要注意的是，通常由正常的L-氨基酸制备的短寡肽不形成稳定的二级结构，而由A_&lt；C_5C&gt；^&lt；DOM&gt；和PIP制备的短寡肽形成单手螺旋。因此，这些结果可能对开发使用折叠体的不对称反应有一定的参考价值。

项目成果

Y.Takano: "Synthesis of cyclic alpha, alpha-disubstituted amino acids bearing gamma-nitrogen atom"Peptide Science 2003. (In press).

Y.Takano：“带有γ-氮原子的环状α、α-二取代氨基酸的合成”肽科学2003。（出版中）。

Concise Synthetic Strategy toward Cyclic α,α-Disubstituted α-Amino acids Bearing a o-Nitrogen Atom : Chiral 1-Substituted 4-Aminopiperidine-4-carboxylic Acids

带有邻氮原子的环状 α,α-二取代 α-氨基酸的简明合成策略：手性 1-取代 4-氨基哌啶-4-羧酸

• 发表时间: 2005
• 期刊: Tetrahedron 61
• 作者: M.Oba;et al.
• 通讯作者: et al.

Computational study on conformation of oligopeptides controlled by side chain chiralities ofα-amino acids

α-氨基酸侧链手性控制寡肽构象的计算研究

• 发表时间: 2005
• 期刊: Peptide Science 2004
• 作者: M.Kurihara;et al.
• 通讯作者: et al.

Controlling the helical screw sense of oligopeptide by chiral cyclic α,α-disubstituted α-amino acid

手性环状α,α-二取代α-氨基酸控制寡肽的螺旋方向

• 发表时间: 2004
• 期刊: Peptide Science 2003
• 作者: N.Tanaka;et al.
• 通讯作者: et al.

Relationship between a-amino acid chiral center and helical secondary structure of its oligopeptides

α-氨基酸手性中心与其寡肽螺旋二级结构的关系

• 发表时间: 2005
• 期刊: Peptide Science 2004
• 作者: M.Tanaka;et al.
• 通讯作者: et al.