a ]-PYRIDINE ] DERIVATIVES AND THEIR INTERESTING BEHAVIOR IN 1 H-NMR SPECTRA IN DEUTERIOCHLOROFORM 1
a ]-PYRIDINE ] DERIVATIVES AND THEIR INTERESTING BEHAVIOR IN 1 H-NMR SPECTRA IN DEUTERIOCHLOROFORM 1
复制标题
a]-吡啶]衍生物及其在氘代氯仿中 1 H-NMR 谱中的有趣行为 1
DOI：
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
Kennosuke Itoh
中科院分区：
文献类型：
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作者：
T. Abe;A. Kakehi,;H. Suga;Y. Okumura;Kennosuke Itoh
在碱存在下，3-[双（甲硫基）亚甲基]-2（3 H）-咪唑并[1，2-a]吡啶酮与4-氯乙酰乙酸乙酯反应，合成了2 '，3'-二氢-2-甲硫基-2 '，4-二氧代螺[2-环戊烯-1，3'-咪唑并[1，2-a]吡啶]-3-羧酸乙酯。这些螺环化合物中的2-甲硫基很容易被伯胺和仲胺取代，得到相应的2-氨基衍生物。非常有趣的是，这些螺环化合物在氘代氯仿（CDCl 3）中的H-NMR谱中的质子信号随着样品浓度的增加而改变，并且对每个质子移动的幅度和方向的分析揭示了该分子中环戊烯酮部分的构象变化。前言咪唑并[1，2-a]吡啶环是合成和天然产物中生物活性分子的核心结构单元。因此，开发一种新的合成路线和结构修饰的这种支架已经深入研究的目的是开发新的活性剂。近年来，2（3 H）-咪唑并[1，2-a]吡啶酮衍生物在3位上带有螺环，具有重要的药理活性。例如，据报道螺[咪唑并-[1，2-a]吡啶-3，2-茚满]-2（3 H）-酮（A，ZSET 1446）可作为阿尔茨海默病进展抑制剂和认知增强剂，螺[环戊烷-1，3-咪唑并[1，2-a]吡啶]-2 '（3' H）酮（B）可作为孕酮受体调节剂（见图1）。不不
Ethyl 2’,3’-dihydro-2-methylthio-2’,4-dioxospiro[2-cyclopentene-1,3’imidazo[1,2-a]pyridine]-3-carboxylates were synthesized from the reactions of 3-[bis(methylthio)methylene]-2(3H)-imidazo[1,2-a]pyridinones with ethyl 4-chloroacetoacetate in the presence of a base. The 2-methylthio group in these spiro compounds was easily replaced with some primary and secondary amines to afford the corresponding 2-amino derivatives. Very interestingly, the proton signals of these spiro compounds in the H-NMR spectra in deuteriochloroform (CDCl3) changed with an increase in the sample concentration, and the analysis for the magnitude and the direction of each proton shift disclosed the conformational change of the cyclopentenone moiety in this molecule. INTRODUCTION For many years, imidazo[1,2-a]pyridine ring has been known to be core structural unit of bioactive molecules in synthetic and natural products. Thus the development of a novel synthetic route and the structural modifications for this scaffold have been intensively investigated with the aim of developing novel active agents. Recently, 2(3H)-imidazo[1,2-a]pyridinone derivatives bearing a spiro ring at the 3-position were shown to possess some important pharmacological activities. For example, spiro[imidazo-[1,2-a]pyridine-3,2-indan]-2(3H)-one (A, ZSET1446) was reported to act as an Alzheimer’s disease progression inhibitor and cognitive enhancer, and spiro[cyclopentane-1,3-imidazo[1,2-a]pyridine]-2’(3’H)one (B) was shown to act as a progesterone receptor modulator (see Figure 1). N N O N N O