Gong Wei, Zhang Guofu, Liu Tao, Giri Ramesh, Yu Jin-Quan
Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
J Am Chem Soc. 2014 Dec 3;136(48):16940-6. doi: 10.1021/ja510233h. Epub 2014 Nov 20.
Although the syntheses of novel and diverse peptides rely mainly on traditional coupling using unnatural amino acids, postsynthetic modification of peptides could provide a complementary method for the preparation of nonproteinogenic peptides. Site selectivity of postsynthetic modification of peptides is usually achieved by targeting reactive moieties, such as the thiol group of cysteine or the C-2 position of tryptophan. Herein, we report the development of site-selective functionalizations of inert C(sp(3))-H bonds of N-terminal amino acids in di-, tri-, and tetrapeptides without installing a directing group. The native amino acid moiety within the peptide is used as a ligand to accelerate the C-H activation reaction. In the long run, this newly uncovered reactivity could provide guidance for developing site-selective C(sp(3))-H activation toward postsynthetic modification of a broader range of peptides.
尽管新型多样肽的合成主要依赖于使用非天然氨基酸的传统偶联方法，但肽的合成后修饰可为非蛋白质ogenic肽的制备提供一种补充方法。肽合成后修饰的位点选择性通常通过靶向反应性基团来实现，例如半胱氨酸的硫醇基团或色氨酸的C-2位。在此，我们报告了在二肽、三肽和四肽中，无需安装导向基团即可对N端氨基酸的惰性C(sp(3))-H键进行位点选择性官能团化的研究进展。肽内的天然氨基酸部分用作配体以加速C-H活化反应。从长远来看，这种新发现的反应性可为开发针对更广泛肽的合成后修饰的位点选择性C(sp(3))-H活化提供指导。
