Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
Carbohydr Res. 2022 Oct;520:108610. doi: 10.1016/j.carres.2022.108610. Epub 2022 Jul 16.
A pyridoneimine-catalyzed oxa-Michael addition of protecting groups-free, native mono- and disaccharides with Michael acceptors in aq. solution is reported. Several mono- and disaccharides are reacted with acceptors, namely, methylvinyl ketone, acrylonitrile and tert-butyl acrylate in aq. solution, the addition catalyzed by n-pentylpyridone imine. The addition occurs site-selectively at the anomeric lactol and the remaining hydroxy functionalities are un-affected. The resulting keto-glycopyranoside products are explored in aldol, allylation and oxime product formation, occurring at either α-methyl moiety or at the keto-moiety, with appropriate synthons. In another direction, the keto-glycopyranoside is functionalized further with amino acids through reductive amination in aq. methanol solution. Formation of hemiacetal anion occurs in the presence of pyridoneimine in aq. Solution, enabling subsequent addition to occur with acceptors. Facile reductive amination of the resulting keto-glycoside provides an avenue for conjugations with amino acids in the present work.
本文报道了一种在水相中，无需保护基团的游离单糖和二糖与迈克尔受体的吡咯烷酮亚胺催化的氧杂-Michael 加成反应。几种单糖和二糖与迈克尔受体（如甲基乙烯基酮、丙烯腈和叔丁基丙烯酰胺）在水相中反应，由正戊基吡咯烷酮亚胺催化。加成反应选择性地发生在糖的端基内酯上，而剩余的羟基官能团不受影响。所得的酮糖苷产物可进一步用于醛醇缩合、烯丙基化和肟产物形成反应，反应可在α-甲基部分或酮部分进行，使用适当的合成子。在另一个方向上，酮糖苷通过在水甲醇溶液中的还原胺化进一步官能化。在水相中存在吡咯烷酮亚胺时会形成半缩醛阴离子，从而使随后与受体的加成反应能够发生。所得酮糖苷的还原胺化反应很容易进行，为本文中与氨基酸的偶联提供了途径。
