阿尔茨海默病(Alzheimer’s disease, AD)是一种与年龄相关的，不可逆转的神经退行性疾病，其中β-淀粉样蛋白(β-amyloid, Aβ)级联假说认为，脑内Aβ斑块作为AD的一种重要病理学特征，在大脑内的形成和积累早于临床症状的出现。因此结合核医学成像技术(如正电子发射断层扫描(Positron Emission Computed Tomography, PET)和单光子发射计算机断层扫描(Single-Photon Emission Computed Tomography, SPECT))，开发以脑内Aβ斑块为靶点且与之具有高亲和力和选择性的分子探针，对于实现AD的早期非侵入性诊断具有重要意义。为了有效降低分子探针的脂溶性，提高其在体内的药代动力学性质，本课题在新型柔性骨架结构的分子基础上，设计并合成了在侧链具有两个手性羟基的分子探针，并利用质谱、氢谱、碳谱等测试方法对两种不同手型构型的化合物进行指认。此外，通过手性柱(High Performance Liquid Chromatography, HPLC)分析的方法对化合物的手性纯度进行验证。体外竞争结合实验表明两种手性构型的化合物与Aβ1-42聚集体具有一定的亲和力，(S, S)和(R, R)构型的Ki分别是0.44 μM和0.32 μM。

Alzheimer's disease (AD) is an age-related, irreversible neurodegenerative disease. The β-amyloid hypothesis indicates that the formation and accumulation of β-amyloid (Aβ) plaques is an essential pathological feature of AD. Furthermore, the formation and accumulation of β-amyloid (Aβ) plaques in the brain precedes the onset of clinical symptoms. Therefore, combining the radioactive imaging probes with molecular imaging techniques (such as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT)), we can develop the radioactive imaging probe with high affinity and selectivity targeting Aβ plaques in the brain which is an effective access to the diagnosis and prognosis of AD.To further reduce the molecular lipophilicity and improve its pharmacokinetic properties, in this study we designed and synthesized a class of flexible probes which have two chiral hydroxyl groups on the side chain, then identified the compounds by mass spectrometry, hydrogen spectrometry, carbon spectrometry and HPLC (High Performance Liquid Chromatography) analysis. The chiral purity of the compound was confirmed by chiral column analysis. The results of in vitro binding assay using Aβ aggregates showed that the Ki value of these two chiral compounds to Aβ aggregates is 0.44 μM and 0.32 μM.