Stereocontrolled synthesis of a potent antimalarial alkaloid, (+)-febrifugine

A novel and stereocontrolled synthetic path to a potential antimalarial piperidine alkaloid, (+)-febrifugine, was established by employing the reductive deamination and simultaneous recyclization of a proline derivative with samarium diiodide, as a key step.     

Evaluation of gas chromatography-tandem quadrupole mass spectrometry for the determination of organochlorine pesticides in fats and oils

A gas chromatography-tandem quadrupole mass spectrometry multi-residue method for the analysis of 19 organochlorine pesticides in fats and oils has been developed. Gel permeation chromatography was employed to remove lipid material prior to GC-MS/MS analysis. Average recoveries of the pesticides spiked at 10 and 50 microg kg(-1) into fish oil, pork fat, olive oil and hydrogenated vegetable oil were typically in the range 70-110% with relative standard deviations generally less than 10%. Calculated limits of detection are between 0.1 and 2.0 microg kg(-1) and results obtained for the analysis of proficiency test materials are in good agreement with assigned values. The higher selectivity of the GC-MS/MS compared to electron capture detection and GC-MS in selective ion monitoring mode allowed unambiguous identification and confirmation of all the target pesticides at low microg kg(-1) levels in fats and oils in a single analysis.     

LC-MS/MS method for the confirmatory determination of aromatic amines and its application in textile analysis

A confirmation method for the determination of 18 aromatic amines originating from azo dyes after reductive cleavage was developed. The method is based on the use of high-performance liquid chromatography/tandem mass spectrometry with atmospheric-pressure chemical ionization. For the identification of the analytes one precursor ion and two daughter ions (multi-reaction monitoring, MRM) were selected and the LC-MS/MS parameters optimized to obtain high sensitivity and selectivity. The linear ranges varied from 0.1–1 to 30–50 g mL^–1 with correlation coefficients of 0.99 or better. The applicability of the method to determine o-tolidine (3,3-dimethylbenzidine) and 3,3-dimethoxybenzidine in textiles following reductive cleavage of acid red 114, trypan blue, and Chicago sky blue 6B was demonstrated.     

Twofold Brook rearrangement-mediated tandem reactions of δ-silyl-γ,δ-epoxy-α,β-unsaturated acylsilanes with a cyanide ion

Reaction of δ-silyl-γ,δ-epoxy-α,β-unsaturated acylsilanes with KCN in the presence of chloro or cyanoformates gives highly functionalized dienol silyl ether derivatives via a twofold Brook rearrangement-induced tandem sequence.     

Sensitive Determination of Felodipine in Human and Dog Plasma by Use of Liquid–Liquid Extraction and LC–ESI–MS–MS

Summary A sensitive and selective liquid chromatographic method coupled with electrospray ionization tandem mass spectrometry (LC–ESI–MS–MS) has been developed for quantification of felodipine in human and dog plasma. Compounds were separated on a 2.0 mm × 150 mm, 5.0 m particle, C₈ column with 1 m m ammonium acetate–acetonitrile, 20:80, pH 6.0, as mobile phase at a flow rate of 200 L min^–1. Nifedipine was used as internal standard. Plasma samples were extracted with diethyl ether, the centrifuged upper layer was evaporated, the residue was reconstituted with mobile phase, and the reconstituted samples were injected. The analytical column lasted for at least 1000 injections. By use of multiple reaction monitoring (MRM) mode in MS–MS felodipine and nifedipine were detected without severe interference from the human or dog plasma matrix. Felodipine produced a protonated precursor ion ([M + H]⁺) at m/z 384 and a corresponding product ion at m/z 338. And internal standard (nifedipine) produced a protonated precursor ion ([M + H]⁺) at m/z 347 and a corresponding product ion at m/z 315. Detection of felodipine in human and dog plasma was accurate and precise, with a limit of quantification of 0.05 ng mL^–1. The method has been successfully applied to preliminary pharmacokinetic study of felodipine in human and dog plasma.     

Towards EPC-syntheses of the structural class of cochleamycins and macquarimicins. Part 3: EPC-syntheses of the β-keto lactone subunits and first attempts towards the syntheses of the pentacyclic antibiotics of this group

Practical EPC-syntheses of δ-substituted-β-keto δ-lactones, subunits of the cochleamycins and macquarimicins, are presented. In consequence Tietze's tandem reaction is employed to combine δ-allyl-β-keto δ-lactone with a hydrindene derivative, the second subunit of these acetogenic antibiotics. Model reactions for the final oxidative radical tandem cyclization reveal that the electrophilic radical cyclizes exclusively in exo-trig fashion. However, with the intended precursor of macquarimicin C allylic hydrogen abstraction thwarted the oxidative radical tandem cyclization.     

A highly enantioselective one-pot synthesis of homoallylic alcohols via tandem asymmetric allyl transfer/olefin cross metathesis

A highly enantioselective one-pot synthesis of linear homoallylic alcohols with terminal ester functionality has been achieved. The reactions were controlled by ordered addition of reagents and catalysts, ensuring complete consumption of aldehyde. The synthetic utility of this strategy has been demonstrated in a short synthesis of a low boiling point intermediate for grahamimycin A.     

Serendipitous synthesis of a ditwistane: a one-step access!

4-tert-Butyl-2-cyclohexen-1-one dimerizes in THF solution via its kinetic enolate, leading to di-tert-butylditwistane 8 in up to 36% yield (−78 °C → room temp., protonolysis, flash chromatography). X-ray crystallography shows that 8 incorporates one R and one S enantiomer of the starting ketone; none of the diastereomeric ditwistanes epi-8, epi’-8 or iso-8 was isolated. This means that the formation of 8 proceeds with mutual kinetic resolution and 100% induced diastereoselectivity.