Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents

We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives

Gas-phase reactivity of protonated 2-oxazoline derivatives: mass spectrometry and computational studies

RATIONALE: Oxazolines have attracted the attention of researchers worldwide due to their versatility as carboxylic acid protecting groups, chiral auxiliaries, and ligands for asymmetric catalysis. Electrospray ionization tandem mass spectrometric (ESI-MS/MS) analysis of five 2-oxazoline derivatives has been conducted, in order to understand the influence of the side chain on the gas-phase dissociation of these protonated compounds under collision-induced dissociation (CID) conditions. METHODS: Mass spectrometric analyses were conducted in a quadrupole time-of-flight (Q-TOF) spectrometer fitted with electrospray ionization source. Protonation sites have been proposed on the basis of the gas-phase basicity, proton affinity, atomic charges, and a molecular electrostatic potential map obtained on the basis of the quantum chemistry calculations at the B3LYP/6-31 + G(d, p) and G2(MP2) levels. RESULTS: Analysis of the atomic charges, gas-phase basicity and proton affinities values indicates that the nitrogen atom is a possible proton acceptor site. On the basis of these results, two main fragmentation processes have been suggested: one taking place via neutral elimination of the oxazoline moiety (99 u) and another occurring by sequential elimination of neutral fragments with 72 u and 27 u. These processes should lead to formation of R+. CONCLUSIONS: The ESI-MS/MS experiments have shown that the side chain could affect the dissociation mechanism of protonated 2-oxazoline derivatives. For the compound that exhibits a hydroxyl at the lateral chain, water loss has been suggested to happen through an E2-type elimination, in an exothermic step. Copyright (C) 2012 John Wiley & Sons, Ltd.FAPESPFAPESPCAPESCAPESCNPqCNP

Mass Spectrometry Nomenclature In Portuguese Language [nomenclaturas De Espectrometria De Massas Em Língua Portuguesa]

In commemoration of the International Year of Chemistry this article presents the normalization and standardization of key terms used in mass spectrometry in Portuguese Language.341018751887Murray, K.M., Boyd, R.K., Eberlin, M.N., Langley, G.J., Li, L., Naito, Y., Standard Definitions of Terms Relating to Mass Spectrometry IUPAC, , http://mass-spec.lsu.edu/msterms/index.php/Main_Page, acessada em Fevereiro 2011http://goldbook.iupac.org/, IUPAC Gold Book, acessada em Agosto 2011http://webbook.nist.gov/chemistry/, National Institute of Standards and Technology - NIST, acessada em Agosto 2011Turecek, F., McLafferty, F.W., (1993) Interpretation of Mass Spectra, , University Science Books: SausalitoNiessen, W.M.A., (2006) Em The Encyclopedia of Mass Spectrometry, , Gross M. L.Caprioli, R. M., eds., Elsevier: OxfordPrice, P., (1991) J. Am. Soc. Mass Spectrom, 2, p. 336http://www.asms.org/, acessada em Agosto 2011Sparkman, O.D., (2006) Mass Spectrometry Desk Reference, , Global View Publishing: PittsburghMallet, A.I., Down, S., (2010) Dictionary of Mass Spectrometry, , John Wiley & Sons, Ltd: ChichesterCole, R.B., (2010) Electrospray and MALDI Mass Spectrometry: Fundamentals Instrumentation Practicalities and Biological Applications, , 2nd ed. John, Wiley & Sons, Inc.: New JerseyWatson, J.T., Sparkman, O.D., (2007) Introduction to Mass Spectrometry: Instrumentation, Applications, and Strategies for Data Interpretation, , Wiley: New Yor

Pharmacokinetic properties, in vitro metabolism and plasma protein binding of govaniadine an alkaloid isolated from Corydalis govaniana Wall

Made available in DSpace on 2018-11-26T17:10:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-11-30Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Council for Scientific and Technological DevelopmentGovaniadine (GOV) is an alkaloid isolated from Corydalis govaniana Wall. It has been reported to show a different number of biological activities including anti-urease, leishmanicidal and antinociceptive. The present study aims to characterize the GOV in vitro metabolism after incubation with rat and human liver microsomes (RLM and HLM, respectively) and to evaluate its pharmacokinetic properties. The identification of GOV metabolites was conducted by different mass analyzers: a micrOTOF II-ESI-ToF Bruker Daltonics (R) and an amaZon-SLion trap (IT) Bruker Daltonics (R). For the pharmacokinetic study of GOV in rats after intravenous administration, a LC-MS/MS method was developed and applied to. The analyses were performed using an Acquity UPLC (R) coupled to an AcquityTQD detector equipped with an ESI interface. The liver microsomal incubation resulted in new O-demethylated, di-hydroxylated and mono-hydroxylated compounds. Regarding the method validation, the calibration curve was linear over the concentration range of 2.5-3150.0 ng mL(-1), with a lower limit of quantitation (LLOQ) of 2.5 ng mL(-1). This method was successfully applied to a pharmacokinetic study. The profile was best fitted to a two-compartment model, the first phase with a high distribution rate constant (alpha) 0.139 +/- 0.086 min(-1), reflected by the short distribution half-life (t1/2 alpha) 9.2 +/- 8.9 min and the later one, with an elimination half-life (t1/2 beta) 55.1 +/- 37.9 min. The main plasma protein binding was 96.1%. This is a first report in this field and it will be useful for further development of govaniadine as a drug candidate. (C) 2016 Elsevier B.V. All rights reserved.Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Quim Fis, BR-14040903 Ribeirao Preto, SP, BrazilKings Coll London, Wolfson Ctr Age Related Dis, Guys Campus, London SE11 UL, EnglandUniv Estadual Paulista, Fac Ciencias Farmaceut Araraquara, Dept Principios At Nat & Toxicol, BR-14801902 Araraquara, SP, BrazilUniv Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Ribeirao Preto, SP, BrazilUniv Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, PakistanTribhuvan Univ, Amrit Sci Campus, Kathmandu, NepalUniv Estadual Paulista, Fac Ciencias Farmaceut Araraquara, Dept Principios At Nat & Toxicol, BR-14801902 Araraquara, SP, BrazilFAPESP: 2013/16496-5FAPESP: 2013/17658-9FAPESP: 2014/13192-8FAPESP: 2014/23604-1National Council for Scientific and Technological Development: 442384/201