Johns Deidre M, Mori Makoto, Williams Robert M
Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA.
Org Lett. 2006 Aug 31;8(18):4051-4. doi: 10.1021/ol061524s.
7-Hydroxy-quinine was synthesized by an asymmetric aldol reaction that establishes the C8 and C9 stereochemistry, followed by construction of the 3-vinyl-quinuclidine azabicyclo[2.2.2]octane by C3-C4 ring closure using an intramolecular palladium-mediated allylic alkylation with excellent regio- and diastereoselectivity. This is the first report of a ketone-enolate-stereocontrolled allylic alkylation mediated by palladium. The title compound and a dehydro-quinine analogue were evaluated for antimalarial activity.
7-羟基奎宁是通过不对称羟醛反应合成的，该反应确定了C8和C9的立体化学，随后通过分子内钯介导的烯丙基烷基化进行C3-C4闭环构建3-乙烯基奎宁环氮杂双环[2.2.2]辛烷，具有优异的区域和非对映选择性。这是钯介导的酮-烯醇化物-立体控制烯丙基烷基化的首次报道。对标题化合物和脱氢奎宁类似物进行了抗疟活性评估。
