Figure 1
From: Metampicillin is a cyclic aminal produced by reaction of ampicillin with formaldehyde
| Ampicillin (1) reacts with formaldehyde (HCHO) to form cyclic aminals (2 and 3). (A) Previously proposed structures for metampicillin (4 and 5) and the metampicillin structure (2) identified in this work by NMR after HPLC purification/lyophilisation. Compound 3 is observed in solution but could not be isolated. 6 is obtained by reaction of 1 with HCHO in acidic conditions (100 °C) as reported9. B/C/D. 1H (700 MHz) spectra of 1 (D), 2 (C) and 3 (B) in D2O. (C) Adding a twofold excess of HCHO to 1 results in 2; trace amounts of 1 and 3 are observed (in brackets). (D) In the presence of excess HCHO, further reaction to give 3 occurs. Structures were assigned using 2D NMR (Figs. S3, S5 and S6). (E) Plot of integrals of the cyclic aminal resonance of 2 (blue) and the hemiaminal resonance of 3 (green) observed during reaction of 1 with a twofold excess of HCHO. (F) Magnified section of the 1H NMR spectra showing both hemiaminal protons (green, “m”) of 3 after reaction of 1 with different amounts of HCHO (4 h). The two overlapping singlets at δH 4.34 ppm are assigned to the CHCO2H hydrogens of 2 (higher field singlet, blue “a”) and 3 (lower field singlet, green “a”). Addition of further HCHO correlates with increased 3 and decreased 2.
