Selective Catalytic Reductions of Amides and Nitriles to Amines

This personal account summarizes our recent developments of catalytic hydrosilylations and hydrogenations of carboxylic amides and nitriles to selectively give amines. Special focus is given to highly chemoselective iron- and zinc-catalyzed reductions of amides.     

Ökonomische Bewertung und Optimierung des Automatisierungsgrades von Versicherungsprozessen

In the context of value and customer orientation there are various requirements concerning the process – especially in insurance companies: processes are meant to be standardized, automated, and flexible. It is in question whether a fast and cheap automated processing is preferred to manual handling. For which claims and which process steps is it of economic value to have the flexibility and the competence and ability to solve problems of human operators at your disposal? Various combinations, representing different degrees of automation, are possible. The different degrees of automation for the processing of an insurance claims are compared and resulting cash flows are determined. It is essential to include all consequences that can be attributed to a single process and to consider customer reactions and restrictions to the capacity of processing. Instead of using heuristic rules to decide on automation in practice, here the decision is flexible and depends on the given situation. Viewing an aggregated number of insurance claims it is possible to deduce information about the performance of the process. The model is exemplarily illustrated with help of a part of the process for handling own damage glass claims.     

Quantile regression of indoor air concentrations of volatile organic compounds (VOC)

There are many factors determining the concentration of volatile organic compounds (VOCs) in indoor air. On the basis of 601 population-based measurements we develop an explicit exposure model that includes factors, such as renovation, furniture, flat size, smoking, and education level of the occupants.As a novel method for the evaluation of concentrations of indoor air pollutants we use quantile regression, which has the advantages of robustness against non-Gaussian distributions (and outliers) and can adjust for unbalanced frequencies of observations. The applied bi- and multivariate quantile regressions provide (1) the VOC burden that is representative for the population of Leipzig, Germany, and (2) an inter-comparison of the effects of the studied factors and their levels.As a result, we find strong evidence for factors of general impact on most VOC components, such as the season, flooring, the type of the room, and the size of the apartment. Other impact factors are very specific to the VOC components. For example, wooden flooring (parquet) and new furniture increase the concentration of terpenes as well as the modifying factors high education and sampling in the child's room. Smokers ventilate their flats in an extent that in general reduces the VOC concentrations, except for benzene (contained in tobacco smoke), which is still higher in smoking than in non-smoking flats. Very often dampness is associated with an increased VOC burden in indoor air.An investigation of mixtures emphasises a high burden of co-occurring terpenes in very small and very large apartments.     

Paenilarvins: Iturin Family Lipopeptides from the Honey Bee Pathogen Paenibacillus larvae

The bacterium Paenibacillus larvae has been extensively studied as it is an appalling honey bee pathogen. In the present work, we screened crude extracts derived from fermentations of P. larvae genotypes ERIC I and II for antimicrobial activity, following the detection of four putative secondary metabolite gene clusters that show high sequence homology to known biosynthetic gene clusters for the biosynthesis of antibiotics. Low molecular weight metabolites produced by P. larvae have recently been shown to have toxic effects on honey bee larvae. Moreover, a novel tripeptide, sevadicin, was recently characterized from laboratory cultures of P. larvae. In this study, paenilarvins, which are iturinic lipopeptides exhibiting strong antifungal activities, were obtained by bioassay‐guided fractionation from cultures of P. larvae, genotype ERIC II. Their molecular structures were determined by extensive 2D NMR spectroscopy, high resolution mass spectrometry, and other methods. Paenilarvins are the first antifungal secondary metabolites to be identified from P. larvae. In preliminary experiments, these lipopeptides also affected honey bee larvae and might thus play a role in P. larvae survival and pathogenesis. However, further studies are needed to investigate their function.     

Modulating Mucin Hydration and Lubrication by Deglycosylation and Polyethylene Glycol Binding

A key property of mucin glycoproteins is their exceptional capacity to hydrate and lubricate surfaces. In vivo, mucins assemble into mucus hydrogels that cover the epithelium and protect it from dehydration and shear stress. A better understanding of the origin of these properties could lead to new treatment strategies for patients with poor mucus coverage, defective mucus production, or glycosylation as caused by Sjögren syndrome, dry eye, or in the case of certain bacterial infections. In this work, mucin coatings are used to show that mucin‐associated glycans are essential for the formation of such hydrated and lubricating layers. Native mucins are compared with deglycosylated mucins by analyzing their hydration and it is shown that their lubricative potential in the boundary and mixed lubrication regime is linked to the hydration. The removal of glycans from the mucin results in a 3.5‐fold decrease in hydration and an increase in friction by two orders of magnitude. This loss of function is countered by grafting polyethylene glycol (PEG) molecules to defective mucins through lectin–glycan interactions. This lectin‐PEG conjugation restores hydration and improves lubrication of the partially deglycosylated mucin coatings. Thus, local complementation of defective mucus layers could prove to be a useful new treatment strategy.     

An Unusual Thioesterase Promotes Isochromanone Ring Formation in Ajudazol Biosynthesis

The ajudazols are antifungal secondary metabolites produced by a hybrid polyketide synthase (PKS)‐nonribosomal peptide synthetase (NRPS) multienzyme “assembly line” in the myxobacterium Chondromyces crocatus Cm c5. The most striking structural feature of these compounds is an isochromanone ring system; such an aromatic moiety is only known from two other complex polyketides, the electron transport inhibitor stigmatellin and the polyether lasalocid. The cyclization and aromatization reactions in the stigmatellin pathway are presumed to be catalyzed by a cyclase domain located at the end of the PKS, while the origin of the lasalocid benzenoid ring remains obscure. Notably, the ajudazol biosynthetic machinery does not incorporate a terminal cyclase, but instead a variant thioesterase (TE) domain. Here we present detailed phylogenetic and sequence analysis, coupled with experiments both in vitro and in vivo, that suggest that this TE promotes formation of the isochromanone ring, a novel reaction for this type of domain. As the ajudazol TE has homologues in several other secondary‐metabolite pathways, these results are likely to be generalizable.     

A Novel Process for Selective Ruthenium‐Catalyzed Oxidation of Naphthalenes and Phenols

Arenes are selectively oxidized to the corresponding quinones employing ruthenium(2,2′,6′:2′′‐terpyridine)(2,6‐pyridinedicarboxylate) [Ru(tpy)(pydic] as catalyst and hydrogen peroxide as the terminal oxidant. Applying alkylated naphthalenes and phenols, benzo‐ and naphthoquinones are obtained in up to 93% yield. The industrially interesting oxidation of 2‐methylnaphthalene gave 74% of the corresponding quinones and 60% of menadione (vitamin K₃). 2,3,5‐Trimethylbenzoquinone which constitutes the key intermediate for vitamin E is obtained in 83% yield.     

Real-time measurement of oligomeric species in secondary organic aerosol with the aerosol time-of-flight mass spectrometer

Real-time detection of oligomers in secondary organic aerosols has been carried out with an aerosol time-of-flight mass spectrometer sampling particles generated in a smog chamber. The photooxidation products of 1,3,5-trimethylbenzene and NOx were studied over a range of initial 1,3,5-trimethylbenzene concentrations (137-1180 ppb), while keeping the 1,3,5-trimethylbenzene to NOx ratio nearly constant. The photooxidation products of a mixture of alpha-pinene (initial concentration 191 ppb), 1,3,5-trimethylbenzene (60 ppb), and NOx were also investigated. In both systems, ions were observed in the single-particle mass spectra up to 750 Da; the species observed differed in the two systems. These high-mass ions occur with characteristic spacing of 14 and 16 Da, indicative of oligomeric species. The results obtained agree well with off-line (matrix-assisted) laser desorption/ionization mass spectrometry results. The real-time capabilities of the aerosol time-of-flight mass spectrometer make it possible to investigate the temporal development of the oligomers with 5-min time resolution and also demonstrate that there are certain ions within the oligomer population that occur in nearly all of the particles and with relatively high signal intensity, suggesting that these ions have higher stability or that the species are formed preferentially.     

Silicon Analogues of the RXR‐Selective Retinoid Agonist SR11237 (BMS649): Chemistry and Biology

C/Si switch : Twofold sila‐substitution (C/Si exchange) in the RXR‐selective retinoids 4 a (SR11237) and 5 a leads to 4 b (disila‐SR11237) and 5 b , respectively. Chemistry and biology of the C/Si pairs are reported.