Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, UK.
School of Natural and Environmental Sciences, Chemistry Bedson Building, Kings Road, Newcastle Upon Tyne, NE1 7RU, UK.
Sci Rep. 2020 Oct 21;10(1):17955. doi: 10.1038/s41598-020-74990-1.
Metampicillin is a β-lactam antibiotic that is prepared by the reaction of ampicillin with formaldehyde. Although metampicillin has been studied for treatment of infections in animals and humans, its structure has been unclear. We report NMR studies revealing that metampicillin contains a formaldehyde-derived cyclic aminal. NMR time-course experiments with excess formaldehyde in solution show formation of another product with an additional exocyclic hemiaminal group formed by reaction with the cyclic aminal nitrogen. The exocyclic hemiaminal group is readily removed by reaction with the formaldehyde scavenger 1,3-cyclohexanedione, whereas the cyclic aminal methylene exhibits greater stability. The overall results assign the structure of metampicillin as containing a cyclic aminal and further reveal the potential for complexity in the reaction of formaldehyde with biomedicinally relevant molecules.
美他培南是一种β-内酰胺抗生素，由氨苄西林与甲醛反应制备。尽管美他培南已被研究用于治疗动物和人类的感染，但它的结构仍不清楚。我们报告了 NMR 研究结果，表明美他培南含有一个甲醛衍生的环状亚胺。在溶液中与过量甲醛进行的 NMR 时程实验表明，形成了另一种产物，其中通过与环状亚胺氮反应形成了另一个额外的外环亚胺基团。通过与甲醛清除剂 1,3-环己二酮反应，很容易去除外环亚胺基团，而环状亚胺亚甲基则表现出更大的稳定性。总体结果表明，美他培南的结构含有一个环状亚胺，并进一步揭示了甲醛与具有医学相关分子反应的复杂性。
