Methyl [13C]Glucopyranosiduronic Acids: Effect of COOH Ionization and Exocyclic Structure on NMR Spin-Couplings

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• 作者：Wenhui Zhang ; Xiaosong Hu ; Ian Carmichael ; Anthony S. Serianni
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：November 2, 2012
• 年：2012
• 卷：77
• 期：21
• 页码：9521-9534
• 全文大小：797K
• 年卷期：v.77,no.21(November 2, 2012)
• ISSN：1520-6904

文摘

Methyl 伪- and 尾-d-glucopyranuronides singly labeled with ¹³C at C1鈥揅6 were prepared from the corresponding ¹³C-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 (²H₂O) 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 ³J_H4,H5, are unaffected by solution pD, and COOH ionization exerts little effect on J_CH and J_CC except for ¹J_C1,H1, ¹J_C4,H4, ¹J_C5,H5, ¹J_C5,C6, and ²J_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鈥揙 bond conformation. Titration of ¹H and ¹³C chemical shifts, and some J-couplings, yielded a COOH pK_a of 3.0 卤 0.1 in both anomers. DFT calculations suggest that substituents proximal to the exocyclic COOH group (i.e., the C4鈥揙4 bond) influence the activation barrier to C5鈥揅6 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 CH₂OH substituent at C6 than from COOH ionization within the uronides. Twelve J-couplings are affected, with the largest being ¹J_C5,C6 (18 Hz larger in the uronides), followed by ²J_C6,H5 (2.5 Hz more negative in the uronides).