A Versatile Annulation Protocol toward Novel Constrained Phosphinic Peptidomimetics
摘要:
[GRAPHICS]The development of a novel 3-center 2-component annulation reaction between alpha,omega-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting alpha,omega-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochernistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structrures.
将乙二胺接头连接到寡胸苷序列的 5' 末端提供了与 K2PtCl4 络合的配体。铂试剂与二氨基寡胸苷的合成后反应生成二氨基二氯铂-DNA 偶联物,可用于通过寡脱氧核苷酸介导的三链体形成进行 DNA 双链体靶向。第三条链和双链体之间的交联只发生在直接参与三链体形成的双链目标链上。没有观察到与互补目标链交联的例子或与两条目标链交联的情况。当二核苷酸 d(GpG) 存在于目标链中并且没有与相应的 7-deazaG 二核苷酸目标发生交联时,发生最有效的交联。当 dC 或 dA 残基存在于目标链中时,甚至单个 dG 残基存在时,也会观察到交联,但在任何情况下都未观察到 dT 残基。三链体形成提供了靶向双链 DNA 特定序列的能力;此处所述类型的共轭物提供了将铂络合物递送到特定 DNA 位点的潜力。