Couve-Bonnaire Samuel, Chou Doug T H, Gan Zhonghong, Arya Prabhat
Chemical Biology Program, Steacie Institute for Molecular Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, Canada, K1A 0R6.
J Comb Chem. 2004 Jan-Feb;6(1):73-7. doi: 10.1021/cc030026x.
With the goal of developing a library synthesis of tetrahydroquinoline-derived natural-product-like small molecules, a practical synthesis of enantiomerically pure tetrahydroquinoline scaffold was achieved. An asymmetric aminohydroxylation reaction was the key step in this strategy. This scaffold was further immobilized onto the solid support for the library generation. The library was obtained from three diversity sites: (i) acylation of the hydroxyl group (R(1)), (ii) coupling of the Fmoc-protected amino acid to the amino group (R(2)), and (iii) amidation of the N-terminal amine group (R(3)).
以开发四氢喹啉衍生的类天然产物小分子库的合成方法为目标，实现了对映体纯四氢喹啉骨架的实用合成。不对称氨基羟基化反应是该策略中的关键步骤。该骨架进一步固定在固相载体上以生成文库。该文库来自三个多样化位点：（i）羟基（R(1)）的酰化，（ii）Fmoc保护的氨基酸与氨基（R(2)）的偶联，以及（iii）N端胺基（R(3)）的酰胺化。
