Amide Cis−Trans Isomerization in Aqueous Solutions of Methyl N-Formyl-d-glucosaminides and Methyl N-Acetyl-d-gl

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• 作者：Xiaosong Hu ; Wenhui Zhang ; Ian Carmichael ; Anthony S. Serianni
• 刊名：Journal of the American Chemical Society
• 出版年：2010
• 出版时间：April 7, 2010
• 年：2010
• 卷：132
• 期：13
• 页码：4641-4652
• 全文大小：438K
• 年卷期：v.132,no.13(April 7, 2010)
• ISSN：1520-5126

文摘

Amide cis−trans isomerization (CTI) in methyl 2-deoxy-2-acylamido-d-glucopyranosides was investigated by ¹H and ¹³C NMR spectroscopy. Singly ¹³C-labeled methyl 2-deoxy-2-formamido-d-glucopyranoside (MeGlcNFm) anomers provided standard ¹H and ¹³C chemical shifts and ¹H−¹H and ¹³C−¹³C spin-coupling constants for cis and trans amides that are detected readily in aqueous solution. Equipped with this information, doubly ¹³C-labeled methyl 2-deoxy-2-acetamido-d-glucopyranoside (MeGlcNAc) anomers were investigated, leading to the detection and quantification of cis and trans amides in this biologically important aminosugar. In comparison to MeGlcNFm anomers, the percentage of cis amide in aqueous solutions of MeGlcNAc anomers is small (23% for MeGlcNFm versus 1.8% for MeGlcNAc at 42 °C) but nevertheless observable with assistance from ¹³C-labeling. Temperature studies gave thermodynamic parameters ΔG°, ΔH°, and ΔS° for cis−trans interconversion in MeGlcNFm and MeGlcNAc anomers. Cis/trans equilibria depended on anomeric configuration, with solutions of α-anomers containing less cis amide than those of β-anomers. Confirmation of the presence of cis amide in MeGlcNAc solutions derived from quantitative ¹³C saturation transfer measurements of CTI rate constants as a function of solution temperature, yielding activation parameters E_act, ΔG°, ΔH°, and ΔS° for saccharide CTI. Rate constants for the conversion of trans to cis amide in MeGlcNFm and MeGlcNAc anomers ranged from 0.02 to 3.59 s⁻¹ over 31−85 °C, compared to 0.24−80 s⁻¹ for the conversion of cis to trans amide over the same temperature range. Energies of activation ranged from 16−19 and 19−20 kcal/mol for the cis → trans and trans → cis processes, respectively. Complementary DFT calculations on MeGlcNFm and MeGlcNAc model structures were conducted to evaluate the effects of an acyl side chain and anomeric structure, as well as C2−N2 bond rotation, on CTI energetics. These studies show that aqueous solutions of GlcNAc-containing structures contain measurable amounts of both cis and trans amides, which may influence their biological properties.