Synthesis and 13C NMR of (trifluoromethyl)hydroxypyrazoles

Reaction of ethyl 4,4,4-trifluoroacetoacetate with methylhydrazine produced not only the previously reported 5-hydroxy-3-(trifluoromethyl)pyrazole 1 but also its unknown isomer the 3-hydroxy-5-(trifluoromethyl)pyrazole 4 . The structure assignments are established based on ¹³C nmr spectra. Compound 1 was converted to 5-chloro-3-(trifluoromethyl)pyrazolecarboxylic acid 3 in two steps.     

Study of human urinary metabolism of fenfluramine using gas chromatography-mass spectrometry

The metabolism of (+/-)fenfluramine, 1-(m-trifluoromethylphenyl)-2-N-ethylpropane, an anoretic agent, was investigated in humans. The analysis method was based on the use of ion-exchange resin extraction, solid-phase purification on the Bond Elut1M C8 cartridge, gradient elution high-performance liquid chromatography, enzymic hydrolysis of conjugates, further purification by Bond Elut C8 cartridge, derivatisation and capillary column gas chromatography-mass spectrometry (GC-MS). After administration of a 1 mg kg-1 oral dose, four metabolites plus unchanged fenfluramine were recovered in the 0-24 h urine from human volunteers and characterised by GC-MS. In the conjugated form, fenfluramine, norfenfluramine and m-trifluoromethylhippuric acid were detected by GC-MS. In the aglycone form, the major metabolite, 1-(m-trifluoromethylphenyl)-1,2-propane diol (fenfluramine diol), was monitored using GC-MS. The mass spectral characteristics of the m-trifluoromethylhippuric acid methyl ester, 1-(m-trifluoromethylphenyl)-1,2-propane ditrifluoracetate derivatives and the norfenfluramine and fenfluramine free base obtained under electron-impact ionization are presented. The metabolism of fenfluramine is discussed including a metabolic pathway in man accounting for the formation of its biotransformation products.     

Automated,high performance,flow-through chemiluminescence microarray for the multiplexed detection of phycotoxins

A novel multiplexed immunoassay for the analysis of phycotoxins in shellfish samples has been developed. Therefore, a regenerable chemiluminescence (CL) microarray was established which is able to analyze automatically three different phycotoxins (domoic acid (DA), okadaic acid (OA) and saxitoxin (STX)) in parallel on the analysis platform MCR3. As a test format an indirect competitive immunoassay format was applied. These phycotoxins were directly immobilized on an epoxy-activated PEG chip surface. The parallel analysis was enabled by the simultaneous addition of all analytes and specific antibodies on one microarray chip. After the competitive reaction, the CL signal was recorded by a CCD camera. Due to the ability to regenerate the toxin microarray, internal calibrations of phycotoxins in parallel were performed using the same microarray chip, which was suitable for 25 consecutive measurements. For the three target phycotoxins multi-analyte calibration curves were generated. In extracted shellfish matrix, the determined LODs for DA, OA and STX with values of 0.5 ± 0.3 μg L⁻¹, 1.0 ± 0.6 μg L⁻¹, and 0.4 ± 0.2 μg L⁻¹ were slightly lower than in PBS buffer. For determination of toxin recoveries, the observed signal loss in the regeneration was corrected. After applying mathematical corrections spiked shellfish samples were quantified with recoveries for DA, OA, and STX of 86.2%, 102.5%, and 61.6%, respectively, in 20 min. This is the first demonstration of an antibody based phycotoxin microarray.     

Z = 50 shell gap near 100Sn from intermediate-energy Coulomb excitations in even-mass 106-112Sn isotopes

Rare isotope beams of neutron-deficient 106,108,110Sn from the fragmentation of 124Xe were employed in an intermediate-energy Coulomb excitation experiment. The measured B(E2,0(1)(+)-->2(1)(+)) values for 108Sn and 110Sn and the results obtained for the 106Sn show that the transition strengths for these nuclei are larger than predicted by current state-of-the-art shell-model calculations. This discrepancy might be explained by contributions of the protons from within the Z = 50 shell to the structure of low-energy excited states in this region.     

Total Syntheses of 11-Acetoxy-4-deoxyasbestinin D, 4-Deoxyasbestinin C,Asbestinin-10, -20, -21 and -23

Six members of the asbestinin family of marine diterpene natural products have been synthesized in an efficient and stereoselective manner from a single oxa-bridged intermediate. Five of these natural products have not been synthesized previously and the structures of four of them have been confirmed as those proposed originally or following revisions to the original structures. The fifth natural product—asbestinin-21—has been shown to be a diastereomer of the compound that had been proposed previously.     

Selective Monofunctionalization Enabled by Reaction‐History‐Dependent Communication in Catalytic Rotaxanes

Selective monofunctionalization of substrates with distant, yet equally reactive functional groups is difficult to achieve, as it requires the second functional group to selectively modulate its reactivity once the first functional group has reacted. We now show that mechanically interlocked catalytic rings can effectively regulate the reactivity of stoppering groups in rotaxanes over a distance of about 2 nm. Our mechanism of communication is enabled by a unique interlocked design, which effectively removes the catalytic rings from the substrates by fast dethreading as soon as the first reaction has taken place. Our method not only led to a rare example of selective monofunctionalization, but also to a “molecular if function”. Overall, the study presents a way to get distant functional groups to communicate with each other in a reaction‐history‐dependent manner by creating linkers that can ultimately perform logical operations at the molecular level.