Stoffwechselprodukte von Mikroorganismen. 174. Mitteilung Eine neue Synthese des Ferrichroms; enantio-Ferrichrom

Metabolites of Microorganisms. A New Synthesis of Ferrichrome; enantio-Ferrichrome The enantiomer of the natural sideramine ferrichrome was synthesized starting from D-ornithine. The cyclohexapeptide (D-Orn)₃-Gly₃ was obtained by conventional methods of polypeptide chemistry. For the oxidation of the δ-amino groups of the D-ornithine residues to hydroxylamino groups the oxaziridine pathway was successful. The final steps - introduction of the acetyl groups and formation of the iron trihydroxamate complex - followed known procedures. The spectroscopic and chromatographic properties of the crystalline product corresponded to those of natural ferrichrome, the optical rotations and CD. curves being opposite. The biological activity of enantio-ferrichrome was similar to that of the natural sideramine.     

First comprehensive investigation of Suzuki couplings of alkenyl nonaflates with aryl and alkenyl boronic acid derivatives by using classical conditions and microwave heating

Alkenyl nonaflates (nonafluorobutanesulfonates) are excellent substrates in a variety of palladium-catalysed coupling reactions. We herein demonstrate that bicyclic nonaflates generated from 8-heterobicyclo[3.2.1]octan-3-one derivatives can be coupled with aryl or alkenyl boronic acids in a very efficient manner. The resulting densely functionalised bicyclic skeletons are highly suitable for further synthetic elaboration. The thermal Suzuki couplings provided the expected products in moderate to good yields. Microwave (MW) irradiation dramatically shortened reaction times and gave superior results. Bisboronic ester 19 was also coupled with bicyclic nonaflates, for example, with 14, and double Suzuki-coupling products, such as 22, were isolated in good yields. We demonstrated the great synthetic potential of aryl-substituted 8-heterobicyclo[3.2.1]octene derivatives, such as 15, by the stereoselective conversion of this compound into highly substituted furanose 31 or substituted pyran derivative 33, which were obtained in short and efficient reaction sequences.     

Having Fun (and Commercial Success) with Josiphos and Related Chiral Ferrocene Based Ligands.

The Josiphos ligand family is arguably one of the most versatile classes of chiral ligands with a wide range of applications, including one of the two largest known enantioselective catalytic hydrogenations. In this personal account, we take a look back at the beginning and describe the role Antonio Togni has played to reach this point and the significance of his contributions for the commercial success, especially concerning today's ligand business of Solvias. This seems a fitting point in time in light of Antonio’s statement on his ETH home page that he ‘is working as a professor at this institution since 1992 (a few more months to go), not looking for a job’ and that the three authors have already retired for some time (H. U. B.) or are about to retire soon (B. P., F. S.).     

Samarium diiodide induced ketyl-(het)arene cyclisations towards novel N-heterocycles

In this tutorial review we discuss recent advances in the field of ketyl-(het)arene cyclisations promoted by samarium diiodide and related processes. Couplings of samarium ketyls with carbon-carbon multiple bonds are perhaps the most useful reactions to create carbocycles and heterocycles of various ring sizes. They have also successfully been exploited for the synthesis of biologically active compounds or natural products. In this article we intend to summarise our diversity orientated approaches towards nitrogen heterocycles and emphasize other approaches with SmI(2) as well as electrochemical cyclisation methods providing similar N-heterocycles. We also briefly discuss our recently published formal total synthesis of strychnine employing a new samarium diiodide induced cascade reaction as key step. All these examples demonstrate the high synthetic potential of samarium ketyl-(het)arene cyclisations for the preparation of various types of important heterocyclic compounds.     

Natural Compounds Isolated from Stachybotrys chartarum Are Potent Inhibitors of Human Protein Kinase CK2

A large number of secondary metabolites have been isolated from the filamentous fungus Stachybotrys chartarum and have been described before. Fourteen of these natural compounds were evaluated in vitro in the present study for their inhibitory activity towards the cancer target CK2. Among these compounds, stachybotrychromene C, stachybotrydial acetate and acetoxystachybotrydial acetate turned out to be potent inhibitors with IC₅₀ values of 0.32 µM, 0.69 µM and 1.86 µM, respectively. The effects of these three compounds on cell proliferation, growth and viability of MCF7 cells, representing human breast adenocarcinoma as well as A427 (human lung carcinoma) and A431 (human epidermoid carcinoma) cells, were tested using EdU assay, IncuCyte^® live-cell imaging and MTT assay. The most active compound in inhibiting MCF7 cell proliferation was acetoxystachybotrydial acetate with an EC₅₀ value of 0.39 µM. In addition, acetoxystachybotrydial acetate turned out to inhibit the growth of all three cell lines completely at a concentration of 1 µM. In contrast, cell viability was impaired only moderately, to 37%, 14% and 23% in MCF7, A427 and A431 cells, respectively.     

Analysis of mass transport limitation during emulsion polymerization using reaction calorimetry and conductivity measurement

The seeded emulsion polymerization of styrene was investigated by reaction calorimetry in combination with conductivity measurements using the RC1e calorimeter (Mettler Toledo). Varying the stirrer speed showed the existence of mass transport limitation in the lower speed range. For the case of using the autoclave HP60 with an anchor stirrer a minimum stirrer speed of 400 rpm is required to be sure of adequate mixing in the reactor.