Characterization of Nineteen Impurities in Roxithromycin by HPLC/TOF and Ion Trap Mass Spectrometry

Nineteen impurities in roxithromycin drug substance made in China were separated and identified by HPLC–MSⁿ (TOF and TRAP) for the further improvement of official monographs in Pharmacopoeias. The fragmentation patterns and structural assignment of these impurities were studied. The column was Shim VP-ODS (250 × 4.6 mm, 5 μm). The mobile phase was 10 m mol L⁻¹ ammonium acetate and 0.1 % formic acid aqueous solution-acetonitrile (62.5:37.5). In positive mode, full scan LC–MS was first performed to obtain the m/z value of the protonated molecules and formulas of all detected peaks on Agilent 6538Q TOF high resolution mass spectrometer. LC–MS-MS and LC–MS-MS–MS were then carried out on the compounds of interest on AB SCIEX 4000 Q TRAP™ composite triple quadrupole/linear ion trap tandem mass spectrometer. The complete fragmentation patterns of nineteen impurities were studied and used to obtain information about the structures of these impurities. The structures of nineteen impurities in roxithromycin drug substance were deduced based on the HPLC–MSⁿ data, in which nine impurities were novel impurities.

     

Nickel-catalyzed synthesis of 9-monoalkylated fluorenes from 9-fluorenone hydrazone and alcohols

A practical protocol was disclosed for the nickel-catalyzed C-alkylation of 9-fluorenone hydrazone with alcohols using t-BuOK as the base, and 9-monoalkylated fluorene derivatives were obtained in good yields under the benign conditions.     

Some Novel Quinone-Type Compounds Containing Arylseleno Groups Derived from Tetrachloro-1, 4-Benzoquinone and 2, 3-Dichloro-1, 4-Naphthoquinone

Tetrachloro-1, 2-benzoquinone and 2, 3-dichloro-1, 4-naphthoquinone react with a series of aryl and alkyl selenolate, generated either by the reaction of Grignard reagents and selenium powder or by the reduction of diselenides with NaBH₄, to give 3, 6-diarylseleno-2, 5-dichloro-1, 4-benzoquinones 3 and 2, 3-diarylseleno-1, 4-naphthoquinones 4 in good yields.     

Novel Synthesis of Aza-phthalimidine Hydroxylactams

A novel and convenient synthetic route for preparing aza-phthalimidine hydroxylactams (5a–j) by N-bromosuccinimide (NBS) was developed. This method involved the substitution reactions of substrates (3a–j) with NBS via unstable intermediate bromides (4a–j) rapidly hydrolyzed into hydroxyl products in the course of the workup process.     

Non-enzymatic hydrogen peroxide sensor based on a gold electrode modified with granular cuprous oxide nanowires

Granular nanowires with a diameter of about 60 nm were fabricated from cuprous oxide (Cu₂O) by an electrochemical method using anodic aluminium oxide as the template. A non-enzymatic sensor for hydrogen peroxide (H₂O₂) was then developed on the basis of a gold electrode modified with Cu₂O nanowires and Nafion. The resulting sensor enables the determination of H₂O₂ with a sensitivity of 745 μA?mM^?1?cm^?2, over a wide linear range (0.25 μM to 5.0 mM), and with a low detection limit (0.12 μM). The results demonstrate that the use of such granular nanowires provides a promising tool for the design of non-enzymatic chemical sensors.

Synthesis of 2-(1-Arylcarbonyl-1-arylazomethylidene)-thiazolidines by the Reaction of 2-(Arylcarbonyl-methylidene)thiazolidines with Diazobenzenes

A variety of 2-(1-arylcarbonyl-1-arylazomethylidene)-thiazolidenes were synthesized in excellent yields by the reaction of 2-(arylcarbonylmethylidene)thiazolidines with diazobenzenes.     

Synthesis of Cholesterylated Thiogalactosides for Gene Delivery

A series of cholesterylated thiogalactosides L₁ –L₆ the cell targeting ligands for gene delivery to hepatocytes, was synthesized. Related poly(ethylene glycol) chain was used as a bridge for the attachment of galactoside on one hydroxyl end, while the other hydroxyl end was linked with cholesterol. This design provided an effective entry for the synthesis of a poly(ethylene glycol) compound with the hepatocyte targeting.     

Synthesis of 3-Trifluoromethyl-Substituted Benzo[f]chromene Derivatives in a One-Pot Reaction

In the presence of 1,8-diazabicycolo[5.4.0]undec-7-ene (DBU) and concentrated H₂SO₄, 2-naphthol reacted smoothly with α,β-unsaturated trifluoromethyl ketones in CH₂Cl₂ at room temperature, affording the 3-trifluoromethyl-substituted benzo[f]chromene derivatives in good to excellent yields in a one-pot reaction.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details].     

Water-Mediated Selective Synthesis of Pyrazolo[1,5-a]quinazolin-5(4H)-ones and [1,2,4]Triazolo[1,5-a]quinazolin-5(4H)-one via Copper-Catalyzed Cascade Reactions

A convenient and sustainable synthesis of pyrazolo[1,5-a]quinazolin-5(4H)-ones and [1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one through copper-catalyzed cascade reactions of 2-bromobenzoates with 1H-pyrazol-5-amines or 1H-1,2,4-triazol-5-amine under ligand-free conditions in water is presented. It is notable that aqueous medium turned out to be crucial for the chemoselective formation of the title compounds. Compared with literature protocols, this new method showed advantages such as simple and sustainable procedure, commercially available starting materials, and convenient reuse of the reaction medium together with the copper catalyst.     

Practical synthesis of C1–8 fragment of autolytimycin via a chelation-controlled diastereoselective addition of diisopropenylzinc to α-methoxy aldehyde

The C1–8 fragment of autolytimycin was synthesized via a reliable 10-step route capable of delivering 41% overall yield at multi-gram scale. As a key step, a chelation-controlled isopropenylation of α-oxygenated aldehydes was established with a reagent combination of diisopropenylzinc, magnesium halide, and a dichloromethane/toluene mixed solvent. Cram-chelate isopropenylation products dominated for aldehydes with a small α-substituents, such as –OMe and –OBn groups, while the Felkin product could be obtained with a bulky –OTBS group.