Maruoka Keiji, Tayama Eiji, Ooi Takashi
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5824-9. doi: 10.1073/pnas.0307725101. Epub 2004 Apr 12.
The asymmetric phase-transfer catalytic alkylation of peptides has been achieved by the use of designed C(2)-symmetric chiral quaternary ammonium bromide 1 as catalyst. Excellent stereoselectivities were uniformly observed in the alkylation with a variety of alkyl halides and the efficiency of the transmission of stereochemical information was not affected by the side-chain structure of the preexisting amino acid residues. This method also enables an asymmetric construction of noncoded alpha,alpha-dialkyl-alpha-amino acid residues at the peptide terminal. Since this chirality can be efficiently transferred to the adjacent amino acid moiety, our approach provides a general procedure not only for the highly stereoselective terminal functionalization of peptides but also for the sequential asymmetric construction of unnatural oligopeptides, which should play a vital role in the peptide-based drug discovery process.
通过使用设计的C(2)对称手性季铵溴化物1作为催化剂，实现了肽的不对称相转移催化烷基化反应。在用各种卤代烃进行烷基化反应时，均观察到了优异的立体选择性，并且立体化学信息的传递效率不受预先存在的氨基酸残基侧链结构的影响。该方法还能够在肽末端不对称构建非编码的α,α-二烷基-α-氨基酸残基。由于这种手性能够有效地转移至相邻的氨基酸部分，因此我们的方法不仅为肽的高度立体选择性末端官能化提供了通用程序，也为非天然寡肽的顺序不对称构建提供了通用程序，这在基于肽的药物发现过程中应发挥至关重要的作用。
