Mechanism for semiquinone formation in the oxygen negative chemical ionization mass spectrometry of 2,3,7,8-tetrachlorodibenzo-p-dioxin

The high toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) has led to the development of selective and highly sensitive quantitative methods for mass spectral analysis. Analytical selectivity has been demonstrated for the oxygen negative chemical ionization (ONCI) reaction of TCDD in an oxygen-rich plasma. While the reaction product (4,5-dichloro-1,2-benzoquinone anion) of 2,3,7,8-TCDD and oxygen is well known, the mechanism of its formation has not been studied thoroughly. In this report the results of a study involving the reaction of ¹⁸O₂ with 2,3,7,8-TCDD under high pressure and low pressure ONCI conditions are reported. A mechanism is proposed which is compatible with the observation that one ¹⁸O atom is incorporated into the product anion.     

Quantification of beta-trace protein and detection of transferrin isoforms in mixtures of cerebrospinal fluid and blood serum as models of rhinorrhea and otorrhea diagnosis

Different mixtures from a serum pool and a cerebrospinal fluid (CSF) pool were used as models to study CSF contamination in secretions by determining two CSF specific proteins: beta-trace protein (beta-TP) and the asialo-transferrin (a-Tf) band which was detected by isoelectric focusing (IEF) with Tf specific immunofixation. Beta-TP and total Tf were measured immunonephelometrically. Secretion/serum ratios of beta-TP content > 2.0 indicated CSF contaminations with > or = 5% (v/v) CSF; this was confirmed by detecting the a-Tf band by IEF. Reliable a-Tf bands were only revealed with secretion/serum rations of Tf contents < 0.1, indicating an interference of major sialo-Tf fractions with the a-TF band detection in the sample. For CSF detection in rhinorrhea and otorrhea, complementary use of beta-TP assay and a-Tf assay is recommended. Preanalytically, dilution or concentration of the sample as well as denaturation of Tf and beta-TP should be prevented by optimizing sample collection.     

Vortex breakdown as a fundamental element of vortex dynamics

This paper presents an extension of an earlier analysis on vortex breakdown in tubes of constant cross section by Keller et al. (1985) to axisymmetric vortex flows in tubes with varying cross-sectional area. A broad investigation into the properties of steady axisymmetric vortex flows is given, insofar as they can be represented by perfect-fluid theory and simple extensions of it. It is argued that the basic physics of such flows, including vortex breakdown phenomena, can be explained with the help of the relatively simple theoretical concepts proposed. Numerical results are presented which show complete flow fields of loss-free transitions in diffusers.     

Determination of bile acids and lysolecithin in artificial and natural gastric juice by HPLC for characterization of antacida

Work-up procedures and HPLC separation systems for determination of taurocholic, glycocholic, chenodeoxycholic, and cholic acids and lysolecithin in artificial and natural gastric juice are described. These compounds are used for testing the binding capacity of antacida to the individual analytes. Work-up is simple, no extraction or filtration being required. The optimized combinations of stationary and mobile phases allow selective and sensitive determination of the respective bile acids in gastric juice. For optimization, the capacity factors of two related bile acids were evaluated for numerous commercial stationary phases. The mechanism of retention is different for free and conjugated bile acids. Special aspects of routine analysis are discussed.     

Practical formal total synthesis of (rac)- and (S)-camptothecin

A practical, efficient and scalable formal total synthesis of (rac)- and (S)-camptothecin is described, which proceeds via the known DE ring building blocks 19 and (S)-19, respectively. The racemic synthesis starts from diethyl oxalate and uses straightforward carbonyl chemistry in order to generate the pyridone ring system. 19 was formed in 8.4% overall yield over 9 linear steps avoiding any chromatographic purification. The asymmetric version of this approach encompassed a diastereoselective Grignard addition to the enantiomerically pure alpha-ketoester 30 in order to generate the (S)-configured quaternary stereocenter. The auxiliary could be recycled in high yield and was successfully reused multiple times. The final steps paralleled the racemic approach. (S)-19 was thus prepared in 9.4% overall yield (er = 95 : 5) over 10 steps.     

Practical formal total syntheses of the homocamptothecin derivative and anticancer agent diflomotecan via asymmetric acetate aldol additions to pyridine ketone substrates

Two practical, efficient, and scalable asymmetric routes to DE ring fragment 7, a key building block in the synthesis of the homocamptothecin derivative diflomotecan 4, are described. The "acetal route" starts from 2-chloro-4-cyanopyridine 8 and represents an enantioselective and optimized modification of the original racemic discovery chemistry synthesis. The inefficient optical resolution procedure was replaced by an efficient asymmetric acetate aldol addition (dr 87:13) to a ketone substrate as the key step generating the (R)-configured quaternary stereocenter with high stereoselectivity. 7 was finally obtained in 8.9% overall yield (er 99.95:0.05) over nine steps, avoiding chromatographic purifications and comparing favorably with the initial procedure. In the related "amide route" starting from 2-chloroisonicotinic acid 41, a secondary amide directing group was used to facilitate the ortho lithiation of the pyridine 3-position. The key step of this protocol again consists of a practical asymmetric acetate aldol addition (dr = 87:13). The DE ring building block 7 was thus obtained in 11.1% overall yield (er > 99.95:0.05) over nine steps requiring only one chromatographic purification.