Browsing by Author "Strohmann, Carsten"

Three new compounds, colletotrichones A-C (1-3), and one known compound, chermesinone B (4a), were isolated from an endophytic fungus, Colletotrichum sp. BS4, harbored in the leaves of Buxus sinica, a well-known boxwood plant used in traditional Chinese medicine (TCM). Their structures were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRMS, ECD spectra, UV, and IR, as well as single-crystal X-ray diffraction, and shown to be azaphilones sharing a 3,6a-dimethy1-9-(2-methylbutanoyl)-9H-furo[2,3-h]isochromene-6,8-dione scaffold. Owing to the remarkable antibacterial potency of known azaphilones coupled to the usage of the host plant in TCM, we evaluated the antibacterial efficacy of the isolated compounds against two commonly dispersed environmental strains of Escherichia coli and Bacillus subtilis, as well as against two human pathogenic clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa. Compound 1 exhibited marked antibacterial potencies against the environmental strains that were comparable to the standard antibiotics. Compound 3 was also active against E. coli. Finally, compound 2a exhibited the same efficacy as streptomycin against the clinically relevant bacterium S. aureus. The in vitro cytotoxicity of these compounds on a human acute monocytic leukemia cell line (THP-1) was also assessed. Our results provide a scientific rationale for further investigations into endophyte-mediated host chemical defense against specialist and generalist pathogens.

A theoretical and experimental study of a three-component one-pot cycloaddition reaction involving unstabilized azomethine ylides and unsymmetrical exocyclic dienones featuring a tetralone core was performed. Two new families of highly substituted dispirooxindolo-pyrrolizidine/pyrrolidines were obtained with moderate to good yields. To rationalize the origin of the reactivity difference between the two exocyclic double bonds of the starting dienones, a topological QTAIM (Quantum theory of Atoms in Molecules) analysis study has been performed. To rationalize the observed regio- and stereoselectivity of the [3+2] cycloaddition, a computational approach was realized by means of density functional theory (DFT) at the B3LYP/6-311G(d,p) level of theory. The calculations corroborate the experimental findings. It was demonstrated that the double bond located at the 3-position of the enone scaffold is more reactive than its analogue at the 1-position and that the aforementioned reaction occurs in a chemoselective manner through a two-step mechanism. Moreover, it progresses under kinetic control to offer a mixture of two dispirooxindolo-pyrrolidines/pyrrolizidines with a high diastereomeric excess. The relative stereochemistry of derivative 4k was confirmed by an X-ray crystallography study. The intermolecular N–H–O hydrogen bonding occurring in the difluorinated spiro-compound 4k has been investigated by Hirshfeld surface analysis. Furthermore, the electronic absorption and fluorescence properties of several derivatives have been studied.

An endophytic fungus, Eupenicillium sp. LG41, isolated from the Chinese medicinal plant Xanthium sibiricum, was subjected to epigenetic modulation using an NAD(+)-dependent histone deacetylase (HDAC) inhibitor, nicotinamide. Epigenetic stimulation of the endophyte led to enhanced production of two hew decalin-containing compounds, eupenicinicols C and D (3 and 4), along with two biosynthetically related known compounds, eujavanicol A (1) and eupeniciincol A (2). The structures and stereochemistry of the new compounds were elucidated by extensive spectroscopic analysis using LC-HRMS, NMR, optical rotation, and ECU calculations, as well as single-crystal X-ray diffraction. Compounds 3 and 4 exist in chemical equilibrium with two and three, cis/trans isomers, respectively, as revealed by LC-MS analysis. Compound 4 was active against Staphylococcus aureus with an MIC of 0.1 mu g/mL and demonstrated marked cytotoxicity against the human acute monocytic leukemia cell line (THP-1). We have shown that the HDAC inhibitor, nicotinamide, enhanced the production of compounds 3 and 4 by endophytic Eupenicillium sp. LG41, facilitating their isolation, structure elucidation, and evaluation of their biological activities.

The stem bark of Polyalthia oliveri was screened for its chemical constituents using liquid chromatography high resolution mass spectrometry resulting in the isolation of three indolosesquiterpene alkaloids named 8 alpha-polyveolinone (1), N-acetyl-8 alpha-polyveolinone (2) and N-acetyl-polyveoline (3), together with three known compounds, dehydro-O-methylisopiline (4), N-methylurabaine (5) and polycarpol (6). The structures of the compounds were elucidated by means of high resolution mass spectrometry and different NMR techniques and chemical transformations. Their absolute configurations were assigned by ab-initio calculation of CD and ORD data (for 2 and 3) and X-ray diffraction analysis (for 2). Compounds 2 and 3 exhibited moderate antiplasmodial activity against erythrocytic stages of chloroquine-sensitive Plasmodium falciparum NF54 strain and low cytotoxicity on rat skeletal myoblast (L6) cell line. (C) 2014 Elsevier Ltd. All rights reserved.

Modern organic synthesis (e.g., of natural products) is virtually impossible without employment of enantiomerically enriched compounds. In many cases, alkyllithium compounds are key intermediates for the generation of these stereogenic substances. In recent years, the lithiated carbon atom in silicon-substituted benzyllithium compounds has become a focus of interest because it is possible to maintain its stereogenic information. Starting from a highly enantiomerically enriched benzylsilane, (R,S)-2.quinuclidine could be obtained, and the absolute configuration at the metalated carbon atom was determined by X-ray diffraction analysis. In solution, a quartet was found in the (13)C NMR spectrum for the metalated carbon atom because of coupling between carbon and lithium, indicating a fixed lithium carbon contact at room temperature. After reaction of (R, S)-2.quinuclidine with trimethylchlorostannane, the trapped product (S,S)-4 was obtained with a dr >= 98:2 with inversion of the configuration at the metalated carbon. Multipole refinement against high-resolution diffraction data and subsequent topological analysis of the benchmark system (R,S)-2.quinuclidine provide insight in the electronic situation and thus the observed stereochemical course of the transformations. Surprisingly, the negative charge generated at the carbanion hardly couples into the phenyl ring. The neighboring silicon atom counterbalances this charge by a pronounced positive charge. Therefore, the a-effect of the silicon atom is caused not just by a polarization of the electron density but also by an electrostatic bond reinforcement. Furthermore, the experimentally determined electrostatic potential unequivocally explains the observed back side attack of an electrophile under inversion of the stereogenic center with high diastereomere ratios.