Application of high-performance liquid chromatography of some antibiotics in clinical microbiology

During recent years high-performance liquid chromatography has become an excellent tool for the determination of antibiotics in biological fluids. Compared with biological assays, the major benefits of this method are specificity and rapidity. In particular, the determination of biologically inactive metabolites emphasizes that this technique plays an outstanding role for the analysis of antibiotics. This paper describes how the method can be used in the analysis of several antibiotics and demonstrates the efficacy of this method for clinical microbiology. Methods for the determination in biological fluids of acylaminopenicillins (azlocillin, mezlocillin, piperacillin and aspoxicillin), quinolones (ciprofloxacine, norfloxacine and ofloxacine), a penem (imipenem) and a cephalosporin (cefixime) are summarized. Furthermore, their application to in vitro studies and their trial in clinical studies are described.     

Simple thiazocine-2-acetic acid derivatives via ring-closing metathesis

A new protocol for synthesis of 2-heterocylylacetic acid derivatives involving conjugate addition of allyl mercaptan to an acrylate containing a tethered olefinic site followed by RCM (ring-closing metathesis) is described. In this series, sulfanyl derivatives were unreactive, while sulfoxide and sulfone analogues provided the corresponding thiazocines in fair to excellent yields. Use of the sulfoxide oxidation state as a protecting group for sulfides inert to RCM is demonstrated also. Thus, oxidation of sulfide 9 [N-allyl-N-[2-(allylthio)-4-(1H-indol-1-yl)-4-oxobutyl]-4-methylbenzenesulfonamide] followed by cyclization yielded the corresponding thiazocine sulfoxide 12. Deprotection (deoxygenation) of 12 was accomplished using Lawesson's reagent, producing 1-[[4-[4-(methylphenyl)sulfonyl]-3,4,5,8-tetrahydro-2H-1,4-thiazocin-2-yl]acetyl]-1H-indole (21) in 67% unoptimized yield.     

Mono- and diboronates derived from tridentate ONO ligands and arylboronic acids

The syntheses of eight [4.3.0] heterobicyclic boronates containing a N → B coordinative bond are described. The monomeric compounds were prepared by reaction of arylboronic acids with a tridentate ligand having the ONO donor set of atoms. It was shown that substituents at the para-position of the B-phenyl moiety transmit electronic effects to the CN bond which in turn is polarized by formation of the N → B coordination bond. At the same time, related tridentate ligands were also reacted with 1,4-benzenediboronic acid in order to prepare benzene diboron complexes. The structure of this type of compounds was confirmed by X-ray analysis for one of the derivatives.     

Novel annulene dications from methylated [2.2]metacyclophane monoenes and [e]-ring benzannelated dimethyldihydropyrene

Tetramethyl- and hexamethyl-substituted [2.2]metacyclophane monoenes (10 and 11) are transformed into their corresponding trans-dimethyldihydroethanophenanthrenium dications (14(2+) and 15(2+)) in FSO(3)H x SbF(5) (4:1) and FSO(3)H x SbF(5) (1:1) with SO(2)ClF or SO(2) as the solvent; these 10 pi-dications are equivalent to the C-4/C-5 diprotonated dications of the 2,7-dimethyl derivative of trans-DMDHP, 3a. The trans-12c,12d-dimethyl-12c,12d-dihydrobenzo[e]pyrene (6) reacts with FSO(3)H/SO(2)ClF under surprisingly mild conditions to give initially a persistent diprotonated dication (6H(2)(2+)) and, subsequently, the oxidation dication (6(2+)); the 6(2+):6H(2)(2+) ratio reaches 4:1 after 1 week at low temperature. Protonation of the anti-metacyclophane (13) was also examined. Charge delocalization mode and tropicity in the resulting dications are gauged via detailed NMR studies at 500 MHz.     

A transannular reaction during the base catalysed rearrangement of bicyclo(4.3.0)-2β-hydroxy-2α-vinyl-1β-Methyl-8-oxo-Δ6,7-nonene

Synthesis and rearrangement of bicyclo(4.3.0) - 2β - hydroxy - 2α - vinyl - 1β - methyl - 8 - oxo - Δ⁶ - nonene was observed to yield a transannular reaction product tricycio - (6.3.0.0^1,8) - 2 - methyl - 8α - hydroxy - 4 - oxo - Δ² - undecene 16. Spectral evidence supports the assigned structure.     

Raney nickel reductions—VIII A synthesis of 1:2-benzanthracene and its 3′-methyl and 4-methyl derivatives

1:2-Benzanthracene and the 3′-methyl derivative have been prepared by Raney nickel reduction of the sulphuric esters of the leuco derivatives of 1:2-benzanthraquinone and 4′-chloro-3′-methyl-1:2-benzanthraquinone, followed by dehydrogenation. 3-Hydroxy-1:2-benzanthraquinone was methylated in the 4-position by formaldehyde, sodium hydrosulphite and sodium hydroxide solution (the Marschalk reaction). Simultaneous reduction of the nuclear hydroxyl and quinone groups was effected by Raney nickel reduction of the trisulphuric ester of 3:9:10-trihydroxy-4-methyl-1:2-benzanthracene, and the resultant hexahydro-4-methyl-1:2-benzanthracene was dehydrogenated to 4-methyl-1:2-benzanthracene. The preparation of 3:4:9:10-dibenzopyrene from Mayvat brilliant red AF by Raney nickel reduction of the sulphuric ester of the leuco derivative and subsequent dehydrogenation is described.     

A convenient preparation of 3,3,3-trifluoro-1-propynylamines and their Lewis acid catalyzed reaction with carbonyl compounds leading to (z)-alpha-(trifluoromethyl)-alpha,beta-unsaturated amides

N,N-Dialkyl(3,3,3-trifluoro-1-propynyl)amines were readily prepared by a three-step procedure starting from commercially available 2,2,3,3,3-pentafluoropropanol. These fluorinated alkynylamines reacted smoothly with a variety of aldehydes or ketones in the presence of a catalytic amount of Lewis acid and molecular sieves 4A at ambient temperature to produce the corresponding alpha-(trifluoromethyl)-alpha,beta-unsaturated amides in good to excellent yields with high Z-stereoselectivity.     

Thick-target PIGE analysis of plant materials preconcentrated by dry ashing

An analytical methodology has been developed for the UV-spectrophotometric determination of carbaryl in waters after its preconcentration onto a polyether type polyurethane foam followed by on-line elution. The aforementioned strategy offers an easy way for in-field sampling and to improve the analytical sensitivity. Several chemical and flow variables (mass of sorbent, sample flow rate, sample volume and carrier flow rate) were studied to ensure the best performance of the system. Recovery studies, carried out on natural water samples spiked with known amounts of carbaryl at concentration levels between 250 and 500 mug l(-1), provided recovery percentages between 94 and 105%. A detection limit of 12 mug l(-1) was achieved and a variation coefficient of 3.4% was obtained at 0.50 mug ml(-1).