Definition of Angular Dependence of 1H-15N Coupling Constants in Amino Sugars

对研究对象氨基糖(天然丰度为15N)的一维1H谱和一维1H-15N Carr-Purcell-Meiom-Gill异核单量子多键相关(CPMG-HSQMBC)谱进行了全面的分析，得到了与分子几何构型相关的3JHCCN偶联常数。这些氨基糖包括细菌多糖中常见的那些，包括D-氨基葡萄糖、D-甘露糖胺和D-氨基半乳糖，在本研究中作为它们的N-乙酰和盐酸盐衍生物。用分子动力学(MD)方法和隐式溶剂能量最小化方法对N-乙酰-D-氨基葡萄糖、N-乙酰-D-甘露糖胺和N-乙酰-D-氨基半乳糖的α-和β-吡喃糖异构体的几何构型进行了计算。这一分子模拟研究得到了与3JHCCN偶合常数测量值相关联的邻近氮-氢二面角(Phi)值。 MD/MM发现常见N-乙酰氨基糖中氢核和氮-15核的Guche排列的phi值在52-66之间，相当于0.8-2.5赫兹的3JHCCN值。在MD/MM中，氢和氮-15核的平移PHI值在175-178范围内，这与3.2-4.0赫兹范围内较大的3JHCCN值相关联。然而，如果耦合涉及反常质子H-1，则反式耦合常数的大小被吡喃糖环氧的电负性减小到2.7-2.8赫兹。因此，3JHCCN偶联常数的大小似乎可以用来区分氨基糖中邻近氮-15质子对的顺向和横向，从而为确定未知结构中氮原子的立体化学构型(轴向或赤道构型)提供了可能性。虽然这些常见的氨基糖模型只包含有限的15N-1H二面角范围，但它们的3JHCCN偶合常数的结果与我们先前根据所测得的有机可溶氨基糖衍生物的结果基本一致，并由此推导出一个Karplus型方程：3JHCCN=3.1Cos2Phi-0.6cos Phi+0.4

The one-dimensional (1D) 1H spectra and 1D 1H-15N Carr-Purcell-Meiboom-Gill heteronuclear single quantum, multiple bond correlation (CPMG-HSQMBC) NMR spectra of the subject amino sugars (with 15N at natural abundance) have been analyzed completely, and the resulting 3JHCCN coupling constants correlated with molecular geometry. These amino sugars comprise those that are commonly present in bacterial polysaccharides, including D-glucosamine, D-mannosamine, and D-galactosamine, in this study as their N-acetyl and hydrochloride derivatives. The geometries of the alpha and beta pyranose anomers of N-acetyl-D-glucosamine, N-acetyl-D-mannosamine, and N-acetyl-D-galactosamine have been defined by molecular dynamics (MD) calculations with energy minimization by molecular mechanics (MM), and implicit solvent. This molecular modeling study yielded values of the vicinal nitrogen-hydrogen dihedral angles (phi) that have been correlated with the measured values of the 3JHCCN coupling constant. Gauche arrangements of the hydrogen and nitrogen-15 nuclei in the common N-acetyl amino sugars were found by MD/MM to have phi values in the range 52-66, which corresponded to 3JHCCN values of 0.8-2.5 Hz. Trans orientations of the hydrogen and nitrogen-15 nuclei displayed phi values in the range 175-178 in MD/MM, which correlated with larger 3JHCCN values in the range 3.2-4.0 Hz. However, if the coupling involves the anomeric proton H-1, then the magnitude of the trans coupling constant is reduced by the electronegativity of the pyranose ring oxygen to 2.7-2.8 Hz. Thus, it appears that the magnitude of the 3JHCCN coupling constant could be used to distinguish gauche and trans orientations of vicinal nitrogen-15proton pairs in amino saccharides, thus offering the possibility of defining the stereochemical configuration (axial or equatorial) of the nitrogen atom in unknown structures. Although these common amino sugar models contain only limited ranges of 15N-1H dihedral angles, the results for their 3JHCCN coupling constants are in general agreement with those measured for the organic-soluble amino sugar derivatives, from which we previously formulated a Karplus-type equation: 3JHCCN = 3.1 cos2 phi - 0.6 cos phi + 0.4