中桥扭曲酰胺在水溶液中的稳定性。
Stability of medium-bridged twisted amides in aqueous solutions.
机构信息
Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott Hall, Room 4070, University of Kansas, Lawrence, Kansas 66045-7582, USA.
出版信息
J Org Chem. 2009 Mar 6;74(5):1869-75. doi: 10.1021/jo802192v.
Abstract
"Twisted" amides containing nonstandard dihedral angles are typically hypersensitive to hydrolysis, a feature that has stringently limited their utility in water. We have synthesized a series of bridged lactams that contain a twisted amide linkage but exhibit enhanced stability in aqueous environments. Many of these compounds were extracted unchanged from aqueous mixtures ranging from the strongly basic to the strongly acidic. NMR experiments showed that tricyclic lactams undergo reversible hydrolysis at extreme pH ranges but that a number of compounds in this structure class are indefinitely stable under physiologically relevant pH conditions; one bicyclic example was additionally water-soluble. We examined the effect of structure on the reversibility of amide bond hydrolysis, which we attributed to the transannular nature of the amino acid analogs. These data suggest that medium-bridged lactams of these types should provide useful platforms for studying the behavior of twisted amides in aqueous systems.
摘要
含有非常规二面角的“扭曲”酰胺通常对水解非常敏感，这一特性严格限制了它们在水中的应用。我们合成了一系列含有扭曲酰胺键的桥环内酰胺，它们在水相环境中表现出增强的稳定性。许多这些化合物在从强碱性到强酸性的水混合溶液中都能保持不变地提取出来。NMR 实验表明，三环内酰胺在极端 pH 值范围内可发生可逆水解，但该结构类别的许多化合物在生理相关 pH 值条件下具有无限稳定性；一个双环实例具有额外的水溶性。我们研究了结构对酰胺键水解可逆性的影响，我们将其归因于氨基酸类似物的跨环性质。这些数据表明，这种类型的中桥环内酰胺应该为研究扭曲酰胺在水相系统中的行为提供有用的平台。
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