Schwarzwalder Gregg M, Scott David R, Vanderwal Christopher D
Department of Chemistry, University of California, 1102 Natural Sciences II, Irvine, CA, 92697-2025, USA.
Department of Physiology, UC Los Angeles/VA Greater Los Angeles Healthcare System, 11310 Wilshire Blvd, Bldg. 113, Rm. 324, Los Angeles, CA, 90073, USA.
Chemistry. 2016 Dec 12;22(50):17953-17957. doi: 10.1002/chem.201604506. Epub 2016 Oct 26.
A concise and stereoselective synthesis of exiguaquinol dessulfate is described. Sequential application of a Diels-Alder cycloaddition, a desymmetrizing aldol addition, and a reductive Heck cyclization established most of the architecture of exiguaquinol, and a carefully choreographed introduction of the polar substituents afforded the title compound; unfortunately, naphthoquinol sulfation could not be achieved to deliver exiguaquinol. Our hypothesis regarding the configurational preference of the N-acyl hemiaminal, which was based upon an analysis of internal hydrogen-bonding interactions with polar functional groups, was proven correct. A late-stage intermediate did not demonstrate bactericidal activity against H. pylori cultures.
描述了一种简洁且立体选择性的去硫酸异喹诺酮的合成方法。通过依次进行狄尔斯-阿尔德环加成反应、去对称化羟醛加成反应和还原赫克环化反应构建了异喹诺酮的大部分结构，并且通过精心设计引入极性取代基得到了目标化合物；遗憾的是，未能实现萘醌硫酸化以得到异喹诺酮。我们基于对与极性官能团的分子内氢键相互作用的分析而提出的关于N-酰基半缩醛构型偏好的假设被证明是正确的。一个后期中间体对幽门螺杆菌培养物没有杀菌活性。
