Catalytic asymmetric claisen rearrangement in natural product synthesis: synthetic studies toward (-)-xeniolide F

[chemical reaction: see text]. The catalytic asymmetric Claisen rearrangement (CAC) of a highly substituted and functionalized alpha-alkoxycarbonyl-substituted allyl vinyl ether has been exploited to gain access to an advanced building block for the projected total synthesis of (-)-xeniolide F, the enantiomer of a xenicane diterpene isolated from a coral of the genus Xenia.     

The NAA system at the reactor BER II clinical analysis of fluorine,calcium, phosphorus and aluminium in bone biopsies,comparison with photon activation analysis and ion sensitive electrode

Over the past few years an irradiation and measuring system has been developed for the reactor BER II at the Hahn-Meitner-Institut. It was to be suited in particular to the neutron activation analysis of biological material via short lived radionuclides. The general characteristics of this equipment and some experimental details as the recycling facility and the device used for measuring the irradiation time, the waiting time and the neutron fluence are described. This equipment was used to determine physiological concentrations of the elements sodium, chlorine, aluminium, phosphorus, fluorine, calcium, copper and selenium in biological material. The results have been compared with those obtained by photon activation analysis or ion sensitive electrode. We report on the clinical analysis of Ca, F, P and Al in the control of the treatment of osteoporosis patients and of patients undergoing haemodialysis over long periods as an example of the application of the apparatus. Arbeitsgruppe Spurenelemente in der Biomedizin     

Two Tags in One Probe: Combining Fluorescence- and Biotin-based Detection of the Trypanosomal Cysteine Protease Rhodesain

Rhodesain is the major cysteine protease of the protozoan parasite Trypanosoma brucei and a therapeutic target for sleeping sickness, a fatal neglected tropical disease. We designed, synthesized and characterized a bimodal activity-based probe that binds to and inactivates rhodesain. This probe exhibited an irreversible mode of action and extraordinary potency for the target protease with a k_inac/K_i value of 37,000 M⁻¹s⁻¹. Two reporter tags, a fluorescent coumarin moiety and a biotin affinity label, were incorporated into the probe and enabled highly sensitive detection of rhodesain in a complex proteome by in-gel fluorescence and on-blot chemiluminescence. Furthermore, the probe was employed for microseparation and quantification of rhodesain and for inhibitor screening using a competition assay. The developed bimodal rhodesain probe represents a new proteomic tool for studying Trypanosoma pathobiochemistry and antitrypanosomal drug discovery.     

Bestimmung von Fluor in Knochen durch Neutronen- und Photonenaktivierungsanalyse

Zusammenfassung Im Rahmen eines Methodenvergleiches wurde der Fluorgehalt identischer Knochenproben durch Neutronen (NAA)- und Photonen (PAA)-Aktivierungsanalyse untersucht. Nach Optimierung der Bestrahlungs- und Me\bedingungen ergibt sich als Nachweisgrenze bei der NAA 3,9 g und bei der PAA 0,3 g. Diese Nachweisgrenzen sind ausreichend, um in einer Knochenbiopsie der Masse 50 mg den minimal zu erwartenden Fluorgehalt von 200 ppm quantitativ zu bestimmen. Der Analysenfehler betrÄgt in diesem Fall bei der NAA ±15% und bei der PAA ±25%. Der Zeitaufwand für die Analyse einer Einzelprobe betrÄgt 1 min (NAA) bzw. 4 h (PAA). Die Regressionsanalyse ergibt einen Korrelationskoeffizienten von 0,96.

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Determination of fluorine in bones by means of neutron and photon activation analysis

For comparison of the two methods the fluorine content was determined in identical bone samples. After optimization of the irradiation and measuring conditions the detection limit was found to be 3.9 g for NAA and 0.3 g for PAA. Both detection limits are sufficient for the quantitative determination of the minimum expected value of 200 ppm fluorine in a bone biopsy sample of 50 mg. In this case the analytical error is ±15% for NAA and ±25% for PAA, respectively. The time necessary for the analysis of a single sample is 1 min (NAA) or 4 h (PAA). The regression analysis yields a correlation coefficient of 0.96.

     

Ester dienolate [2,3]-Wittig rearrangement in natural product synthesis: diastereoselective total synthesis of the triester of viridiofungin A, A2, and A4

[structure: see text] An ester dienolate [2,3]-Wittig rearrangement was utilized to access the alkylated citric acid skeleton 6 that is characteristic for the viridiofungins and other members of the alkyl citrate family of secondary natural products. The [2,3]-sigmatropic rearrangement of (Z,Z)-15 provided the rearrangement product (+/-)-syn-16 in moderate yield and with very good diastereoselectivity. A Julia-Kocienski olefination efficiently served to connect the polar head (+/-)-syn-26 with the lipophilic tail (32a-c) of the viridiofungins. Amide formation between the racemic viridiofungin precursors 35a-c and the enantiomerically pure amino acid L-tyrosine methyl ester followed by preparative reversed-phase HPLC provided the isopropyl dimethyl ester of viridiofungin A ((+)-39a), A2 ((+)-39b), and A4 ((+)-39c) as well as the nonnatural diastereomers (-)-38a-c.     

Partially Fluorinated Heterocycles from 4,4-Bis(trifluoromethyl)-hetero-1,3-dienes via C–F Bond Activation – Synthesis of 2-Fluoro-3-(trifluoromethyl)furans

An efficient synthesis of 2-fluoro-3-(trifluoromethyl)furans was developed. Keystep of the reaction sequence is a [4 + 1] cycloaddition reaction of tin(II)chloride to 4,4-bis(trifluoromethyl)-1-oxabuta-1,3-dienes. At elevated temperatures the tin heterocycles are transformed into 1-aryl-4,4-difluoro-3-(trifluoromethyl)but-3-en-1-ones which on treatment with sodium hydride in dry DMF give 2-fluoro-3-(trifluoromethyl)furans. The single fluorine bound to C-(2) can be readily replaced by various N-, O-, S-, and C-nucleophiles and dinucleophiles.     

Sulfinylimine: Wichtige neue Bausteine zur Entwicklung der Chemie der Polysulfanmono- und -disulfonsäuren

Sulfinylimines: Important Building Blocks for Developing the Polysulfanemonoand -disulfonic Acid Chemistry Besides hydrolysis of perfluoroorganosulfanesulfinylimines in closed systems, reactions of R_fS_xCl with K₂S₂O₅ or M₂S₂O₃ are also productive methods for the preparation of perfluoroorganosulfanemonosulfonates. The free acid CF₃SSSO₃H is made by treating the potassium salt with a strong acidic cation resin. It is unstable and shows a pK_s-value of approx. –0,5 providing an acidity comparable with polyphosphoric acids. Metathetical reactions of the potassium salts with [(C₆H₅)₄M]Cl (M = P, As) or [R₄N][ClO₄] (R = n-C₃H₇, n-C₄H₉) respectively lead to well crystallized salts. Single crystals are used for x-ray structure analysis. These prove the polysulfanesulfon-moiety to be present in these molecules. Sulfur-sulfur-bonds can also be evidenced by chlorolysis reactions. Not only with Cl₂ but also with SCl₂ R_fS_xCl or R_fS_x+1Cl and ClSO₂OM are formed respectively. In this way CF₃SSSCl is prepared for the first time. The reaction of CF₃SeBr and K₂S₂O₅ provides K[CF₃SeSO₃] which is unstable and decomposes to CF₃SeSeCF₃, K₂S₂O₆, SO₂ and KBr. When S₂Cl₂ is reacted with (CH₃)₃SiNSO besides the main product S₂(NSO)₂ also minor amounts of S_x(NSO)₂ (x = 3, 4, 5) are formed. While hydrolysis of S₂(NSO)₂ leads quantitively to (NH₄)₂S₄O₆, a mixture of ammoniumpolysulfanedisulfonates are obtained from S_x(NSO)₂ which could not be separated. It is demonstrated that chemical reactivity is dominated by disproportionation of S₂(NSO)₂ into S(NSO)₂ and sulfur. Additonal sulfinylimines are obtained by metathesis of XNSO (X = Cl, Br) and AgSCN or AgSeCN respectively. The structures of S₂(NSO)₂ and OSNSCN are established by x-ray methods. By spectroscopical evidence it is shown that OSNSeCN is isostructured with OSNSCN.     

Desorption of hydrogen from an electrode surface under influence of an external magnetic field – In-situ microscopic observations

The effect of a magnetic field in the perpendicular-to-electrode configuration on the hydrogen evolution reaction (HER) was investigated during the deposition of Co. An enhanced desorption of hydrogen in the form of numerous small bubbles was found by combining potentiostatic investigations, coupled with an electrochemical quartz crystal microbalance (EQCM), and simultaneous microscopic observations of the electrode surface. The results are consistent with the recently proposed qualitative model [J.A. Koza, M. Uhlemann, A. Gebert, L. Schultz, Electrochem. Commun. 10 (2008) 1330].