Development of a thin-layer chromatographic method for the enantioresolution of sotalol using levofloxacin as chiral selector

JPC – Journal of Planar Chromatography – Modern TLC - In this work, a commercially available, chirally pure pharmaceutical containing carboxylic group, namely, levofloxacin was utilized...     

Versatility of Alternative Reaction Media: Water-Mediated Domino and Green Chemical Synthesis of Pyrimido[1,2-a]benzimidazole Under Nonconventional Conditions

A convenient and clean water-mediated synthesis of a series of 4-amino-2-aryl-1,2-dihydro pyrimido[1,2-a]benzimidazoles (4) is reported using alternative nonconventional energy sources. The products are obtained in shorter times with excellent yields (78–89%) from the multicomponent reaction of 2-aminobenzimidazole (1), malononitrile/ethylcyanoacetate (2a/b), and carbonyl compounds (3). The reaction is found to be general with respect to the cyclic and acyclic carbonyl compounds. The procedure does not involve the use of any additional reagent/catalyst, produces no waste, and represents a green synthetic protocol with high atom economy.     

Microwave‐assisted facile synthesis of propargylamine library by robust nitro functionalized cross‐linked polystyrene resin supported Cu NPs

In the present investigation, we study catalytic activity of copper nanoparticles stabilized onto a nitro functionalized polystyrene resin (Cu NPs@ Nitro‐Resin). The size of stabilized copper nanoparticles was found between 3 and 9 nm. This work reports a cost‐effective and sustainable protocol for the synthesis of propargylamines. Herein, we have developed microwave‐assisted synthesis of propargylamine from 3 components coupling of aldehyde, alkynes, and amines (A³ coupling) in truly heterogeneous catalytic system. Reaction parameters, such as solvent, catalyst concentration reaction time, and recyclability, were investigated, and reaction conditions were optimized. The present method has advantages such as environmentally benign, ease to handle, short reaction time (≈25 min), excellent yields (98%), low E‐factor (0.15), and high atom economy (94%).     

Development of Nitroreductase-Activatable Fluoroquinolone Prodrugs Exhibiting Attenuated Magnesium Ion Binding

Fluoroquinolones such as levofloxacin and ciprofloxacin are potent antibiotics prescribed to treat various bacterial infections. Recent studies have also identified prominent examples as promising anti-cancer agents. However, significant off-target effects observed in human patients have precluded their wide-spread clinical use. For instance, upon systemic administration, overt toxicity toward eukaryotic organelles (i. e., mitochondria) can result to the destruction of healthy tissue. Moreover, fluoroquinolones feature a β-ketoacid motif which binds to and strips magnesium ions from cartilage, leading to rupture of the Achilles tendon. In this study, we have masked the β-ketoacid of levofloxacin and ciprofloxacin (as well as two quinolones) with a nitroreductase (NTR)-responsive warhead appended through a new self-immolative prodrug linker. The resulting β-ketoester functional group was found to be remarkably resistant toward spontaneous hydrolysis, esterase activity, as well as other ester-cleaving enzymatic systems. Further testing also reveal no cross-reactivity against commonly encountered biologically relevant analytes (e. g., ROS and thiols). Importantly, we demonstrate that upon esterification, the binding toward magnesium ions was attenuated based on an in vitro fluorescent competition assay with the unmodified parent drug.