Resolution of enantiomers of ketoprofen by HPLC: a review

Today, a heightened awareness of the applicability of enantiomers in medicine and clinical practice has been gene-rated due to the continuous evolvement of the field of chirality. In this context, this article provides a review of separation of ketoprofen, an important drug, in a popular class of non-steroidal anti-inflammatory drugs (i.e. profens). This review highlights various methodologies, logistical considerations for separation and provides an exhaustive list of applications mainly focusing on the pharmacokinetic aspects. Clearly, the application of enantioselective methods for drug racemates paves the way to understand the in vivo behavior of individual enantiomer and hence an opportunity for an alternate and/or better option for treating the disease.     

Efficient, selective deprotection of aromatic acetates catalyzed by Amberlyst-15 or iodine

Aromatic acetates were selectively deprotected in the presence of aliphatic acetates to the corresponding phenols in excellent yields using Amberlyst-15 or iodine as catalysts in methanol at room temperature. The first catalyst can be recovered.     

Novel conformationally locked inositols: from aromatics to annulated cyclitols

A new family of ring-annulated inositols with "locked" conformations has been designed to deliver a range of these biologically important entities in "unnatural conformations" while retaining their "natural configurations". The simple "tool" of trans ring fusion has been used to "lock" the conformation of the annulated inositols. Short, simple syntheses of a range of these novel cyclitols have been achieved from readily available aromatic precursors such as tetralin and indane. Along the way, annulated C(2)-symmetric cyclohexadiene-trans-diol (trans-CHD) derivatives have been prepared for the first time and serve as the pivotal building blocks for generating the oxy-functionalization pattern of inositols. The presence of chemo-differentiated hydroxyl groups in our novel inositols is expected to facilitate the installation of phosphate diversity to harness the biological potential of these entities.     

Microwave‐assisted synthesis of new isoxazolyl triazinethiones and isoxazolyl oxadiazinethiones in dry media

Trimolecular condensation of N‐(3‐meihyl‐5‐styryl‐isoxazol‐4‐yl)‐N'‐aryl thioureas ( 2 ), paraformaldehyde and primary amines using montmorillonite K‐10 in dry media under microwave irradiation leads to isoxazolyl triazinethiones ( 3 ) in high yield. Condensation of 2 with paraformaldehyde alone under similar conditions provide isoxazolyl oxadiazinethiones ( 4 ) in excellent yield.     

Simultaneous determination of itraconazole and hydroxyitraconazole in human plasma by high-performance liquid chromatography

The development and validation of a high-performance liquid chromatography (HPLC) method for the simultaneous determination of itraconazole and its metabolite, hydroxyitraconazole, in human plasma is described. The method involved liquid-phase extraction of itraconazole and hydroxyitraconazole using a hexane-dichloromethane (70:30) mixture, after addition of loratidine as an internal standard (IS). Separation was achieved with a reversed-phase C18 column (250 mm x 4.6 mm) employing fluorescence detection (excitation: 264 nm, emission: 380 nm). The mobile phase consisted of [0.01% triethylamine solution adjusted to pH 2.8 with orthophosphoric acid-acetonitrile (46:54)]-isopropanol (90:10, v/v) at a flow rate of 1.0 ml/min. For both the drug and metabolite, the standard curve was linear from 5.0 to 500 ng/ml with goodness of fit (r2) greater than 0.98 observed with four precision and accuracy batches during validation. An observed recovery was more than 70% for drug, metabolite and internal standard. The applicability of this method to pharmacokinetic studies was established after successful application during 35 subjects bioavailibity study. The method was found to be precise, accurate and specific during the study.     

Development and validation of a highly sensitive LC‐MS/MS method for simultaneous quantitation of nortriptyline and 10‐hydroxynortriptyline in human plasma: application to a human pharmacokinetic study

A highly sensitive and specific LC‐MS/MS method has been developed for simultaneous estimation of nortriptyline (NTP) and 10‐hydroxynortriptyline (OH‐NTP) in human plasma (250 µL) using carbamazepine as an internal standard (IS). LC‐MS/MS was operated under the multiple reaction‐monitoring mode using the electrospray ionization technique. A simple liquid–liquid extraction process was used to extract NTP, OH‐NTP and IS from human plasma. The total run time was 2.5 min and the elution of NTP, OH‐NTP and IS occurred at 1.44, 1.28 and 1.39 min, respectively; this was achieved with a mobile phase consisting of 20 mm ammonium acetate : acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a HyPURITY C₁₈ column. The developed method was validated in human plasma with a lower limit of quantitation of 1.09 ng/mL for both NTP and OH‐NTP. A linear response function was established for the range of concentrations 1.09–30.0 ng/mL (r > 0.998) for both NTP and OH‐NTP. The intra‐ and inter‐day precision values for NTP and OH‐NTP met the acceptance as per FDA guidelines. NTP and OH‐NTP were stable in a battery of stability studies, i.e. bench‐top, auto‐sampler and freeze–thaw cycles. The developed assay was applied to a pharmacokinetic study in humans. Copyright © 2010 John Wiley & Sons, Ltd.     

Electroorganic synthesis of 6-aminonicotinic acid from 2-amino-5-chloropyridine

A synthesis of 6-aminonicotinic acid by electrochemical hydrogenation of 5-chloro-2-nitropyridine and electrochemical carboxylation of 2-amino-5-chloropyridine at a cathode surface in the presence of sulphuric acid and carbon dioxide in a dimethylformamide (DMF) solution at an apparent current density of 10 mA/cm² using an undivided cell with good yields is reported.     

Novel Synthesis of 1,2,3,4-Tetrahydropyrazino[1,2-a]indoles

Condensation of 2-(3-methyl-1H-indol-1-yl)ethylamine (7) with benzotriazole and formaldehyde gave 2-(1H-1,2,3-benzotriazol-1-ylmethyl)-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole (8) in 96% yield. Nucleophilic substitutions of the benzotriazolyl group in 8 with NaBH(4), NaCN, triethyl phosphite, allylsilanes, silyl enol ether and Grignard reagents afforded novel 10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indoles 9a-i in 78-95% yields.     

Higher-alcohols biorefinery

The concept of a biorefinery for higher-alcohol production is to integrate ethanol and methanol formation via fermentation and biomass gasification, respectively, with, conversion of these simple alcohol intermediates into higher alcohols via the Guerbet reaction. 1-Butanol results from the selfcondensation of ethanol in this multistep reaction occurring on a single catalytic bed. Combining methanol with ethanol gives a mixture of propanol, isobutanol, and 2-methyl-1-butanol. All of these higher alcohols are usefulas solvents, chemical intermediates, and fuel additives and, consequently, have higher market values than the simple alcohol intermediates. Several new catalysts for the condensation of ethanol and alcohol mixtures to higher alcohols were designed and tested under a variety of conditions. Reactions of methanol ethanol mixtures gave as high as 100% conversion of the ethanol to form high yields of isobutanol with smaller amounts of 1-propanol, the amounts in the mixture depending on the starting mixture. The most successful catalysts are multifunctional with basic and hydrogen transfer components.