Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556-5670, United States.
J Org Chem. 2012 Nov 2;77(21):9521-34. doi: 10.1021/jo3011182. Epub 2012 Oct 23.
Methyl α- and β-D-glucopyranuronides singly labeled with (13)C at C1-C6 were prepared from the corresponding (13)C-labeled methyl D-glucopyranosides, and multiple NMR J-couplings (J(HH), J(CH), and J(CC)) were measured in their protonated and ionized forms in aqueous ((2)H(2)O) solution. Solvated density functional theory (DFT) calculations of J-couplings in structurally related model compounds were performed to determine how well the calculated J-couplings matched the experimental values in saccharides bearing an ionizable substituent. Intraring J(HH) values in both uronide anomers, including (3)J(H4,H5), are unaffected by solution pD, and COOH ionization exerts little effect on J(CH) and J(CC) except for (1)J(C1,H1), (1)J(C4,H4), (1)J(C5,H5), (1)J(C5,C6), and (2)J(C3,C5), where changes of up to 5 Hz were observed. Some of these changes are associated with changes in bond lengths upon ionization; in general, better agreement between theory and experiment was observed for couplings less sensitive to exocyclic C-O bond conformation. Titration of (1)H and (13)C chemical shifts, and some J-couplings, yielded a COOH pK(a) of 3.0 ± 0.1 in both anomers. DFT calculations suggest that substituents proximal to the exocyclic COOH group (i.e., the C4-O4 bond) influence the activation barrier to C5-C6 bond rotation due to transient intramolecular H-bonding. A comparison of J-couplings in the glucopyranuronides to corresponding J-couplings in the glucopyranosides showed that more pervasive changes occur upon conversion from a COOH to a CH(2)OH substituent at C6 than from COOH ionization within the uronides. Twelve J-couplings are affected, with the largest being (1)J(C5,C6) (∼18 Hz larger in the uronides), followed by (2)J(C6,H5) (∼2.5 Hz more negative in the uronides).
Methyl α- 和 β-D-吡喃葡萄糖苷分别用 13C 标记在 C1-C6 位，由相应的 13C 标记的甲基 D-吡喃葡萄糖苷制备，并在质子化和去质子化形式下在水（2H2O）溶液中测量其多个 NMR J 耦合（JHH、JCH 和 JCC）。对结构相关模型化合物中 J 耦合的溶剂化密度泛函理论（DFT）计算，以确定在带有可电离取代基的糖中，计算出的 J 耦合与实验值的吻合程度。在两种呋喃糖苷的内环 JHH 值中，包括（3）J（H4，H5），不受溶液 pH 值的影响，COOH 电离除了对 JCH 和 JCC 有影响外，除了（1）J（C1，H1）、（1）J（C4，H4）、（1）J（C5，H5）、（1）J（C5，C6）和（2）J（C3，C5），观察到高达 5 Hz 的变化。这些变化中的一些与电离时的键长变化有关；一般来说，对于对外环 C-O 键构象不太敏感的耦合，理论与实验之间的一致性更好。（1）H 和（13）C 化学位移的滴定以及一些 J 耦合得到两个呋喃糖苷中 COOH 的 pKa 为 3.0±0.1。DFT 计算表明，与外环 COOH 基团（即 C4-O4 键）相邻的取代基会影响 C5-C6 键旋转的活化能垒，因为存在瞬态的分子内氢键。将吡喃葡萄糖苷中的 J 耦合与相应的吡喃葡萄糖苷中的 J 耦合进行比较表明，与呋喃糖苷中 COOH 离子化相比，将 COOH 转化为 C6 上的 CH2OH 取代基时会发生更广泛的变化。有 12 个 J 耦合受到影响，其中最大的是（1）J（C5，C6）（在呋喃糖苷中约大 18 Hz），其次是（2）J（C6，H5）（在呋喃糖苷中更负约 2.5 Hz）。
