Ulrich Groth

Adenosine analogue nucleosides are a fundamental part of medicinal chemistry. Tubercidin is a well‐known example, but its application is limited due to high toxicity. The development of less toxic synthetic analogues is therefore highly desirable. Here we show the synthesis of fluorinated nucleosides based on the pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) motif. The synthetic approach is based on an easily accessible trifluoromethylated acetoacetate and several amidines, as building blocks. This allows for simultaneous introduction of a CF₃ group as well as a variety of C2 substituents for the synthesis of the heterocyclic part, including alkyl, aryl, SMe, Cl, N₃ and NH₂ moieties. Glycosylation of the fully pre‐functionalized heterocycles proceeds with excellent β‐selectivity. Cytotoxicities were determined using an AlamarBlue assay with HeLa S3 and Hep G2 cancer cell lines. The effect of C2 substitution was explored and a lead structure candidate with IC₅₀ values of 90 ± 49 nM (HeLa S3) and 28 ± 9 nM (Hep G2) was identified.

We present HiTSEE (High-Throughput Screening Exploration Environment), a visualization tool for the analysis of large chemical screens used to examine biochemical processes. The tool supports the investigation of structure-activity relationships (SAR analysis) and, through a flexible interaction mechanism, the navigation of large chemical spaces. Our approach is based on the projection of one or a few molecules of interest and the expansion around their neighborhood and allows for the exploration of large chemical libraries without the need to create an all encompassing overview of the whole library. We describe the requirements we collected during our collaboration with biologists and chemists, the design rationale behind the tool, and two case studies on different datasets. The described integration (HiTSEE KNIME) into the KNIME platform allows additional flexibility in adopting our approach to a wide range of different biochemical problems and enables other research groups to use HiTSEE.

In an attempt to design molecular optoelectronic switches functioning in molecular junctions between two metal tips, we synthesized a set of photochromic compounds by extending the π‐system of 1,2‐bis‐(2‐methyl‐5‐formylfuran‐3‐yl)perfluorocyclopentene through suitable coupling reactions involving the formyl functions, thereby also introducing terminal groups with a binding capacity to gold. Avoiding the presence of gold‐binding sulphur atoms in the photoreactive centre, as they are present in the frequently used analogous thienyl compounds, the newly synthesized compounds should be more suitable for the purpose indicated. The kinetics of reversible photoswitching of the new compounds by UV and visible light was quantitatively investigated in solution. The role of conformational flexibility of the π‐system for the width of the UV/Vis spectra was clarified by using quantum chemical calculations with time‐dependent (TD)‐DFT. As a preliminary test of the potential of the new compounds to serve as optoelectronic molecular switches, monolayer formation and photochemical switching on gold surfaces was observed by using surface plasmon resonance.

A cobalt(I)‐mediated convergent and asymmetric total synthesis of angucyclinones with an aromatic B ring has been developed. In the course of our research, we synthesized three naturally occurring anguclinone derivatives, namely, (+)‐rubiginone B₂(1), (−)‐8‐O‐methyltetrangomycin (2), and (−)‐tetrangomycin (3). By combining 3‐hydroxybenzoic acid, 3‐methoxybenzoic acid, citronellal, and geraniol as starting materials in a convergent way, we were able to synthesize chiral triyne chains, which were cyclized with [CpCo(C₂H₄)₂] (Cp=cyclopentadienyl) by means of an intramolecular [2+2+2] cycloaddition to their corresponding tetrahydrobenzo[a]anthracenes. Successive oxidation and deprotection steps led to the above‐mentioned natural products1–3.

O-Protected cyanohydrins were found to serve as a source of the nitrile within the intramolecular cobalt-mediated [2+2+2] cycloaddition to pyridines. Several 6-substituted 1,2,3,4,7,8,9,10-octahydrophenanthridines were synthesized using this cycloaddition of diyne-cyanohydrins. By introduction a TMS group a divergent way to such phenanthridine derivatives was elaborated.

The scientific literature detailing the synthesis of chroman-2-ones by hydrogenation/reduction of the corresponding coumarins is reviewed. The following methods are described: hydrogenation on palladium, platinum, nickel, catalytic transfer hydrogenation, homogeneous hydrogenation, reduction by complex hydrides, reduction by metals, and electrochemical reduction. For each appropriate reaction, the yield, duration and some additional information is given (if available). Moreover, many exceptions and interesting transformations are described. 1 Introduction 2 Hydrogenation of Coumarins 3 Transfer Hydrogenation of Coumarins 4 Reduction of Coumarins with Metals 5 Reduction of Coumarins with Complex Hydrides 6 Homogeneous Hydrogenation of Coumarins 7 Electrochemical Reduction 8 Other Methods of Coumarin Reduction 9 Conclusion

The coupling of the homocuprate of the bislactim ether of cyclo‐(‐L‐Val‐Gly‐) (9) with primary propargyl halides produces the allenyl‐substituted bislactim ethers 11 in a highly diastereoselective manner, whereas the alkylation of the lithiated bislactim ether of cyclo‐(‐L‐Val‐Gly‐) yields the propargyl‐substituted bislactim ethers 12. Subsequent hydrolysisaffords, after protection of the amino group, the methyl α‐allenylglycinates 15, the α‐allenylglycines 16, and the methyl α‐propargylglycinates 17. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Catalytic homogeneous hydrogenation of 7-methoxy-3-phenylchromone and other substrates was achieved in the presence of cationic iridium complexes and base as co-catalyst. Contrary to common alkene hydrogenation, which is inactivated by base, the hydrogenation of the above set of electron-deficient alkenes turned out to be base-activated.

The functionalized N-benzyl-protected bromoanilines underwent an asymmetric intramolecular carbolithiation in the presence of t-BuLi and (-)-sparteine yielding 3,3-disubstituted indolines. Asymmetric Carbolithiations, Part II; for part I, see reference 10b.