Abstract：
Macrocycles play vital roles in supramolecular chemistry and chromatography. 1,1\'-Bi-2-naphthol (BINOL)-based chiral polyimine macrocycles are an emerging class of chiral macrocycles that can be constructed by one-step aldehyde-amine condensation of BINOL derivatives with other building blocks. These macrocycles exhibit good characteristics, such as facile preparation, rigid cyclic structures, multiple chiral centers, and defined molecular cavities, that make them good candidates as new chiral recognition materials for chromatographic enantioseparations. In this study, a BINOL-based [2+2] chiral polyimine macrocycle was synthesized by one-step condensation of enantiopure (S)-2,2\'-dihydroxy-[1,1\'-binaphthalene]-3,3\'-dicarboxaldehyde with (1R,2R)-1,2-diaminocyclohexane. The product was modified with 5-bromo-1-pentene and then attached to thiolated silica using click chemistry to construct a new chiral stationary phase (CSP). The enantioselectivity of the new CSP was explored by separating various racemates under normal phase (NP) and reversed phase (RP) high performance liquid chromatography (HPLC). Thirteen racemates and eight racemates were enantioseparated under the two separation modes, respectively, including chiral alcohols, phenols, esters, ketones, amines, and organic acids. Among them, nine racemates achieved baseline separation under NP-HPLC and seven racemates achieved baseline separation under RP-HPLC. High resolution separation was observed with benzoin (Rs = 5.10), epinephrine (Rs = 4.98), 3-benzyloxy-1,2-propanediol (Rs = 4.42), and 4,4\'-dimethylbenzoin (Rs = 4.52) in NP-HPLC, and with 4-methylbenzhydrol (Rs = 4.72), benzoin ethyl ether (Rs = 3.79), 1-phenyl-1-pentanol (Rs = 3.68), and 1-(3-bromophenyl)ethanol (Rs = 3.60) in RP-HPLC. Interestingly, the CSP complemented Chiralcel OD-H, Chiralpak AD-H, and CYCLOBOND I 2000 RSP columns for resolution of these test racemates, separating several racemic compounds that could not be well separated by the three commercially available columns. The influences of injected sample amount on separation were also evaluated. It was found that the column exhibited excellent stability and reproducibility after hundreds of injections, and the relative standard deviations (n = 5) of the retention time and resolution were less than 0.49% and 0.69%, respectively. This study indicates that the BINOL-based chiral macrocycle has great potential for HPLC enantioseparation.
摘要：
大环在超分子化学和色谱中起着至关重要的作用。基于1,1'-Bi-2-萘酚（BINOL）的手性聚亚胺大环是一类新兴的手性大环，可以通过BINOL衍生物与其他结构单元的一步醛-胺缩合来构建。这些大环表现出良好的特性，例如容易的准备，刚性循环结构，多个手性中心,和定义的分子腔，使它们成为色谱对映体分离的新型手性识别材料的良好候选物。在这项研究中,通过对映体纯的（S）-2,2'-二羟基-[1,1'-联萘]-3,3'-二甲醛与（1R，2R)-1,2-二氨基环己烷。产物用5-溴-1-戊烯改性,然后使用点击化学连接到硫醇化二氧化硅以构建新的手性固定相(CSP)。通过在正相（NP）和反相（RP）高效液相色谱（HPLC）下分离各种外消旋体来探索新CSP的对映选择性。13种外消旋体和8种外消旋体在两种分离模式下对映体分离,分别,包括手性醇，酚类物质,酯类,酮,胺，有机酸。其中,9种外消旋体在NP-HPLC下实现基线分离，7种外消旋体在RP-HPLC下实现基线分离。用安息香观察到高分辨率分离（Rs=5.10），肾上腺素（Rs=4.98），3-苄氧基-1,2-丙二醇（Rs=4.42），和4,4'-二甲基苯偶姻（Rs=4.52）在NP-HPLC中，和4-甲基苯并氢（Rs=4.72），安息香乙醚（Rs=3.79），1-苯基-1-戊醇（Rs=3.68），和1-(3-溴苯基)乙醇(Rs=3.60)在RP-HPLC中。有趣的是,CSP补充ChiralcelOD-H，ChiralpakAD-H,和CYCLOLOBONDI2000RSP柱，用于解析这些测试外消旋体，分离几种外消旋化合物，这些化合物不能通过三个市售色谱柱很好地分离。还评估了注入样品量对分离的影响。发现该柱在数百次注射后表现出优异的稳定性和再现性，保留时间和分辨率的相对标准偏差(n=5)分别小于0.49%和0.69%,分别。这项研究表明，基于BINOL的手性大环在HPLC对映体分离中具有巨大的潜力。
