Synthesis and antibacterial activity of novel 11,12-cyclic carbonate azithromycin
4-O-carbamate derivatives
Chenchen Ma, Zhaopeng Liu, Hualong Song, Rentao Jiang, Fawen He, Shutao Ma*
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University,
44, West Culture Road, Jinan 250012, P. R. China
Supplementary material
Index:
Synthetic Procedures
S2
IR, 1H NMR and MS Spectra
S3–S10
S1
2′- O-Acetyl-4-O-acylimidazolyl azithromycin 11,12-cyclic carbonate (6)
Compound 6 was prepared from intermediate 2 according to the procedures17 reported
by Ma S., et al. The crude 6 was purified by flash chromatography
(dichloromethane–methanol, 20 : 1) to afford 6 (92.1%) as white solid: mp 117–120
°C; TLC Rf = 0.62 (dichloromethane–methanol, 10 : 1); ESI-MS m/z calculated for
C45H74N4O15 911.1; found (M+H)+ 912.4.
General methods for 11,12-cyclic carbonate azithromycin 4″-carbamate
derivatives (7a–h)
To a solution of 6 (1.33 g, 1.50 mmol) in DMF (15 ml) was added DBU (0.33 ml,
2.25 mmol) and corresponding amine (2.25 mmol). The resulting solution was stirred
for 10 h at the room temperature. The reaction was quenched with water (30 ml) and
the aqueous layer was extracted with ethyl acetate (3 × 15 ml). The combined organic
layers were washed with brine (3 × 15 ml), and dried over anhydrous Na2SO4,
filtered. The filtrate was concentrated in vacuo to afford a crude product.
A solution of the above crude product in methanol (15 ml) was heated to 55 °C
and stirred for 24 h at the same temperature. After concentrating the reaction solution
in
vacuo,
the
residue
was
purified
by
flash
chromatography
(dichloromethane–methanol, 20 : 1) to afford products 7a–h in yields ranging from
68.5% to 80.7%.
17. Ma, S., Jiao, B., Liu, Z., Wang, H., Xian, R., Zheng, M., Lou, H. Synthesis and antibacterial
activity of 4,11-di-O-arylalkylcarbamoyl azithromycin derivatives that have activity against
resistant strains. Bioorg. Med. Chem. Lett. 19, 1698–1701 (2009).
S2
IR, 1H-NMR and MS Spectra of Compound 7a
S3
IR, 1H-NMR and MS Spectra of Compound 7b
S4
IR, 1H-NMR and MS Spectra of Compound 7c
S5
IR, 1H-NMR and MS Spectra of Compound 7d
S6
IR, 1H-NMR and MS Spectra of Compound 7e
S7
IR, 1H-NMR and MS Spectra of Compound 7f
S8
IR, 1H-NMR and MS Spectra of Compound 7g
S9
IR, 1H-NMR and MS Spectra of Compound 7h
S10