Siderophore Biosynthesis Inhibitors

Synthesis and Pharmacokinetic Evaluation of Siderophore Biosynthesis Inhibitors for Mycobacterium tuberculosis

“…Global deprotection with 80% aqueous TFA furnished sulfamide 4 that was purified by reverse-phase HPLC and isolated in 65% yield as the triethylammonium salt. Compound 5 was prepared in an analogous fashion ( 15 → 17 → 18 → 5 ) except sulfamide 15 was acylated with benzyloxycarbonyl (Cbz) protected p -aminosalicylate ( 32 ) 43 employing in situ activation with carbonyl diimidazole (CDI) 25, 33 to afford 17 . Sequential hydrogenolysis of the Cbz group with Pd/C in methanol to 18 followed by acidic deprotection furnished 5 .…”

“…The nucleosides 2′-deoxy-2′-fluoroguanosine 33 and 2′-deoxy-2′-fluoroadenosine 42 were obtained from Metkinen Chemistry (Kuopio, Finland). Compounds 1 , 28 11 , 39 14 , 39 19 , 34 23 , 35 26 , 59 27 , 59 29 , 40 30 , 44 31 , 32 32 , 43 and N -hydroxysuccinimidyl 2-benzyloxybenzoate 28 were prepared as described. All final compounds ( 1–10 ) were purified by preparative reverse-phase HPLC using the indicated method and purity (≥95%) of the lyophilized powders was confirmed by analytical reverse-phase HPLC.…”

“…1 H NMR (400 MHz, CD 3 OD) δ 1.21 (t, J = 7.3 Hz, 14H, excess Et 3 N), 2.98 (q, J = 7.3 Hz, 10H, excess Et 3 N), 3.35−3.30 (ovlp m, 1H), 3.47 (dd, J = 13.5, 3. 5′-O-tert-Butyldimethylsilyl-2′-deoxy-2′-fluoroadenosine (43). 50 To a stirring solution of 42 (0.750 g, 2.8 mmol, 1.0 equiv) in DMF (25 mL) at 0 °C was added sequentially TBSCl (0.462 g, 4.5 mmol, 1.6 equiv) and imidazole (0.322 g, 4.7 mmol, 1.7 equiv).…”

Sulfamic Acid and Its N- and O-Substituted Derivatives

“…The acylsulfamate analog 169 of luciferyl-AMP is a stable and potent analog of firefly luciferase . Some years ago a review on the potential of nucleoside inhibitors based on 5′- O -[ N -(salicyl)sulfamoyl]adenosine (Sal-AMS), 170 (R = OH, X = Na and R = H, X = H), as novel antibiotics targeting siderophore biosynthesis and covering synthesis, physiochemical properties, metabolism, and biological activity, etc., appeared covering the literature into 2006 . A structure–activity study of new derivatives indicates the importance of the aryl ring and the positioning of substituents.…”