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

设计了两种具有光学活性的环α、α-二取代α-氨基酸。一种是具有环戊烷环的二取代氨基酸（A_<C_5C>^<dOM>），另一种是具有哌啶骨架的二取代氨基酸（Pip）。两种环二取代氨基酸具有相似的特点，α-碳原子不是不对称中心，而是在氨基酸的环侧链上存在手性中心。以l -酒石酸二甲酯为手性源合成了A_<C_5C>^<dOM>，以丙二酸二甲酯和手性胺为手性源合成了Pips。作为一种多肽折叠体，采用液相法制备了含有A_<C_5C>^<dOM>和Pip的同肽类和异肽类。在溶液（水和TFE溶液）和固体状态下研究了寡肽的二级结构。结果表明，具有侧链手性中心的（S，S）- a_ <C_5C>^<dOM>同肽在α-位置上没有不对称中心，在溶液和固体状态下均可形成左旋3_<10->和α-螺旋。需要注意的是，通常由正常l -氨基酸制备的短寡肽不形成稳定的二级结构，而由A_<C_5C>^<dOM>和Pip制备的短寡肽形成单手螺旋结构。因此，这些结果可能对利用文件夹的不对称反应的发展有价值。

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.