01042nas a2200169 4500008004100000022001400041245010500055210006900160260011000229300001400339490000600353520031500359100001800674700002900692700002100721856013000742 2012 eng d a2046-206900aGreen synthetic route to antimalarial and antibacterial agent CJ-15,801 and its isomer cis-CJ-15,8010 aGreen synthetic route to antimalarial and antibacterial agent CJ aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcMAR a3596-35980 v23 a

An efficient and rapid synthesis of antiplasmodial and antibacterial agent CJ-15,801 and its isomer cis-CJ-15,801 is disclosed. We have made an attempt towards ``Ideal Synthesis'' or a step towards ``Dial-a-Molecule'' by reducing the number of steps, following atom economy, and a green synthetic route.

1 aKashinath, K.1 aSwaroop, Pandrangi, Siva1 aReddy, Srinivasa uhttp://library.ncl.res.in/content/green-synthetic-route-antimalarial-and-antibacterial-agent-cj-15801-and-its-isomer-cis-cj-001339nas a2200253 4500008004100000022001400041245013000055210006900185260007700254300001400331520038900345653001700734653001300751653002600764653001400790653002200804100002500826700001700851700002400868700002100892700002400913700002100937856012700958 2014 eng d a1434-193X00aGeneral approach to N-heterocyclic carbenes with a fused tetracyclic core: ligands for suzuki-miyaura cross-coupling reaction0 aGeneral approach to Nheterocyclic carbenes with a fused tetracyc aBOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANYbWILEY-V C H VERLAG GMBHcJUL a4482-44863 a

The synthesis of an N-heterocyclic carbene (NHC) based on a tetracyclic scaffold by using simple, general, and scalable chemistry is disclosed. The developed route is suitable for introducing multiple substitutions on the tetracyclic scaffold. The utility of the present NHC as a ligand in the Suzuki-Miyaura cross-coupling reaction is demonstrated with a low catalyst loading.

10aC-C coupling10acarbenes10aHomogeneous catalysis10aN ligands10asynthetic methods1 aSutar, Revannath, L.1 aKumar, Vinod1 aShingare, Rahul, D.1 aThorat, Shridhar1 aGonnade, Rajesh, G.1 aReddy, Srinivasa uhttp://library.ncl.res.in/content/general-approach-n-heterocyclic-carbenes-fused-tetracyclic-core-ligands-suzuki-miyaura-003044nas a2200229 4500008004100000245017800041210006900219260000800288300001400296490000700310520219500317100001502512700001602527700001902543700002302562700002102585700001902606700002102625700002502646700001702671856012602688 2016 eng d00aGSH Induced controlled release of levofloxacin from a purpose-built prodrug: luminescence response for probing the drug release in escherichia coli and staphylococcus aureus0 aGSH Induced controlled release of levofloxacin from a purposebui cSEP a2062-20700 v273 a

Fluoroquinolones are third-generation broad spectrum bactericidal antibiotics and work against both Gram-positive and Gram-negative bacteria. Levofloxacin (L), a fluoroquinolone, is widely used in anti-infective chemotherapy and treatment of urinary tract infection and pneumonia. The main pathogen for urinary tract infections is Escherichia colt, and Streptococcus pneumoniae is responsible for pneumonia, predominantly a lower respiratory tract infection. Poor permeability of L leads to the use of higher dose of this drug and excess drug in the outer cellular fluid leads to central nervous system (CNS) abnormality. One way to counter this is to improve the lipophilicity of the drug molecule, and accordingly, we have synthesized two new Levofloxacin derivatives, which participated in the spatiotemporal release of drug via disulfide bond cleavage induced by glutathione (GSH). Recent studies with Streptococcus mutants suggest that it is localized in epithelial lining fluid (ELF) of the normal lower respiratory tract and the effective [GSH] in ELF is similar to 430 mu M. E. coli typically cause urinary tract infections and the concentration of GSH in porcine bladder epithelium is reported as 0.6 mM for a healthy human. Thus, for the present study we have chosen two important bacteria (Gram + ve and Gram - ve), which are operational in regions having high extracellular GSH concentration. Interestingly, this supports our design of new lipophilic Levofloxacin based prodrugs, which released effective drug on reaction with GSH. Higher lipophilicity favored improved uptake of the prodrugs. Site specific release of the drug (L) could be achieved following a glutathione mediated biochemical transformation process through cleavage of a disulfide bond of these purpose-built prodrugs. Further, appropriate design helped us to demonstrate that it is possible also to control the kinetics of the drug release from respective prodrugs. Associated luminescence enhancement helps in probing the release of the drug from the prodrug in bacteria and helps in elucidating the mechanistic pathway of the transformation. Such an example is scarce in the contemporary literature.

1 aPal, Suman1 aRamu, Vadde1 aTaye, Nandaraj1 aMogare, Devraj, G.1 aYeware, Amar, M.1 aSarkar, Dhiman1 aReddy, Srinivasa1 aChattopadhyay, Samit1 aDas, Amitava uhttp://library.ncl.res.in/content/gsh-induced-controlled-release-levofloxacin-purpose-built-prodrug-luminescence-response