Karle J M, Karle I L
Department of Pharmacology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Acta Crystallogr C. 1992 Nov 15;48 ( Pt 11):1975-80. doi: 10.1107/s0108270192002373.
9-Epiquinine hydrochloride dihydrate [(9S)-6'-methoxycinchonan-9-ol hydrochloride dihydrate], C20H25N2O2+.Cl-.2H2O, M(r) = 396.9, orthorhombic, P212121, a = 8.059 (2), b = 11.537 (3), c = 22.311 (6) A, V = 2074.1 (9) A3, Z = 4, Dx = 1.271 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 18.58 cm-1, F(000) = 848, room temperature, final R = 6.56% for 1344 reflections with magnitude of Fo > 3 sigma (F). 9-Epiquinine crystallized as a hydrated tertiary amine hydrochloride salt. The intramolecular N(1)+ ...O distance is 2.816 A. All H atoms attached to O or N atoms form intermolecular hydrogen bonds. The Cl ion is involved in four hydrogen bonds including one with the hydroxyl group of 9-epiquinine. The N(1)+-H moiety hydrogen bonds to a water molecule. The O(12)-C(9)...N(1)+-H(1) torsion angle was equal to -0.2 (3.8) degrees in comparison to 97.0 degrees for quinidine sulfate [Karle & Karle (1981). Proc. Natl Acad. Sci. USA, 78, 5938-5941]. Two theories have been proposed in the literature to explain the low antimalarial activity of 9-epiquinine. The crystal structure of 9-epiquinine hydrochloride is not consistent with the hypothesis that 9-epiquinine prefers to form intramolecular rather than intermolecular hydrogen bonds, but is consistent with the hypothesis that N(1) and the hydroxyl group of 9-epiquinine are in an orientation which is unfavorable towards exerting antimalarial activity.
9-表奎宁盐酸盐二水合物[（9S）-6'-甲氧基金鸡纳-9-醇盐酸盐二水合物]，C20H25N2O2 +.Cl-.2H2O，M（r） = 396.9，正交晶系，P212121，a = 8.059（2），b = 11.537（3），c = 22.311（6）Å，V = 2074.1（9）Å3，Z = 4，Dx = 1.271 g cm-3，Cu Kα，λ = 1.54178 Å，μ = 18.58 cm-1，F（000） = 848，室温，对于1344个|Fo|>3σ（F）的反射，最终R = 6.56%。9-表奎宁以水合叔胺盐酸盐的形式结晶。分子内N（1）+...O距离为2.816 Å。所有与O或N原子相连的H原子形成分子间氢键。Cl离子参与四个氢键，其中一个与9-表奎宁的羟基形成氢键。N（1）+-H部分与一个水分子形成氢键。与硫酸奎尼丁[卡尔勒和卡尔勒（1981年）。美国国家科学院院刊，78，5938 - 5941]的97.0°相比，O（12）-C（9）...N（1）+-H（1）扭转角等于-0.2（3.8）°。文献中提出了两种理论来解释9-表奎宁的低抗疟活性。9-表奎宁盐酸盐的晶体结构与9-表奎宁更倾向于形成分子内而非分子间氢键的假设不一致，但与9-表奎宁的N（1）和羟基处于不利于发挥抗疟活性的取向的假设一致。
