Graduate School of Biomedical Sciences, Nagasaki University , 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Osaka University of Pharmaceutical Sciences , Osaka 569-1094, Japan.
J Org Chem. 2016 Aug 5;81(15):6343-56. doi: 10.1021/acs.joc.6b00982. Epub 2016 Jul 20.
Helical peptide foldamer catalyzed Michael addition reactions of nitroalkane or dialkyl malonate to α,β-unsaturated ketones are reported along with the mechanistic considerations of the enantio-induction. A wide variety of α,β-unsaturated ketones, including β-aryl, β-alkyl enones, and cyclic enones, were found to be catalyzed by the helical peptide to give Michael adducts with high enantioselectivities (up to 99%). On the basis of X-ray crystallographic analysis and depsipeptide study, the amide protons, N(2)-H and N(3)-H, at the N terminus in the α-helical peptide catalyst were crucial for activating Michael donors, while the N-terminal primary amine activated Michael acceptors through the formation of iminium ion intermediates.
报道了螺旋肽折叠体催化硝基烷或二烷基丙二酸酯与α,β-不饱和酮的迈克尔加成反应，并对其对映诱导的机理进行了考虑。研究发现，多种α,β-不饱和酮，包括β-芳基、β-烷基烯酮和环状烯酮，都可以被螺旋肽催化生成具有高对映选择性（高达 99%）的迈克尔加成产物。基于 X 射线晶体学分析和去酰胺肽研究，α-螺旋肽催化剂中 N 端的酰胺质子，N(2)-H 和 N(3)-H，对于激活迈克尔供体至关重要，而 N 端的伯胺通过形成亚胺离子中间体来激活迈克尔受体。
