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The first total synthesis of chondrochloren A is accomplished using a 1,2-metallate rearrangement addition as an alternative for the Nozaki-Hiyama-Kishi reaction. This transformation also avoids the inherent challenges of this polyketide segment and provides a new, unprecedented strategy to assemble polyketidal frameworks. The formation of the Z-enamide is accomplished using a Z-selective cross coupling of the corresponding amide to a Z-vinyl bromide., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Myxobacteria are well-established sources for novel natural products exhibiting intriguing bioactivities. We here report on haprolid (1) isolated from Byssovorax cruenta Har1. The compound exhibits an unprecedented macrolactone comprising four modified amino acids and a polyketide fragment. As configurational assignment proved difficult, a bioinformatic analysis of the biosynthetic gene cluster was chosen to predict the configuration of each stereocenter. In-depth analysis of the corresponding biosynthetic proteins established a hybrid polyketide synthase/nonribosomal peptide synthetase origin of haprolid and allowed for stereochemical assignments. A subsequent total synthesis yielded haprolid and corroborated all predictions made. Intriguingly, haprolid showed cytotoxicity against several cell lines in the nanomolar range whereas other cells were almost unaffected by treatment with the compound., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The tedanolides are biologically active polyketides that exhibit a macrolactone constructed from a primary alcohol. Since polyketidal transformations only generate secondary alcohols, it has been hypothesized by Taylor that this unique lactone could arise from a postketidal transesterification. In order to probe this hypothesis and to investigate the biological profile of the putative precursor of all members of the tedanolide family, we embarked on the synthesis of desepoxyisotedanolide and its biological evaluation in comparison to desepoxytedanolide. The biological experiments unraveled a second target for desepoxytedanolide and provided evidence that the proposed transesterification indeed provides a survival advantage for the producing microorganism., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ekkehard Winterfeldt, who was President of the Gesellschaft Deutscher Chemiker (German Chemical Society; GDCh) from 1996-1997 passed away on October 11, 2014. His research achievements included the synthesis of alkaloids and steroids, and stereoselective transformations. He was known as a gentleman and an inspiring scholar, and was able to convey his passion for science to everybody who worked with him., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Here we describe the synthesis of β-lipomycin, a secondary metabolite isolated from the fermentation broth of Corallococcus coralloides. The synthesis relies on the structural assignment made by a statistical method, the so-called profile hidden Markov model. Using this protocol, not only the configuration of the secondary alcohol, but also of the adjacent methyl branch could be deduced. The synthesis therefore not only provides access to this natural product but also confirms the validity of this approach for configurational assignment at methyl branches of modular polyketides., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The impressive biological profile of secondary metabolites isolated from strains of Sorangium cellulosum prompted us to initiate synthetic studies on kulkenon, also isolated from Sorangium cellulosum. The synthesis features a syn-selective vinylogous Kobayashi aldol reaction, recently developed by us, and a ring-closing intramolecular Heck reaction as the pivotal transformations. Comparison of the NMR spectra of the authentic and synthetic material revealed that the proposed configuration had to be revised. A combination of molecular modeling and NOE experiments was used to propose the revised configuration, which was confirmed by a new synthesis., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Synthesis can provide molecules such as paleo-soraphens A and B that are genetically encoded but not obtained from the natural source. Although it is unclear whether this is part of an evolutionary process or the consequence of the chemical synthesis, the biological evaluation of these genetically encoded natural products can shed light on how natural products are structurally optimized with respect to their biological profile., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Shortly after the discovery of the proteasome it was proposed that inhibitors could stabilize proteins which ultimately would trigger apoptosis in tumor cells. The essential questions were whether small molecules would be able to inhibit the proteasome without generating prohibitive side effects and how one would derive these compounds. Fortunately, "Mother Nature" has generated a wide variety of natural products that provide distinct selectivities and specificities. The chemical synthesis of these natural products finally provided access to analogues and optimized drugs of which two different classes have been approved for the treatment of malignancies. Despite these achievements, additional lead structures derived from nature are under investigation and will be discussed with regard to their biological potential and chemical challenges., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Leading the way: the synthesis of natural products with new biological targets is one of the driving forces for the development of new antibiotics. The synthesis of the two secondary metabolites corallopyronin and myxopyronin have been achieved, which are prominent leads for the inhibition of bacterial RNA polymerase., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Covalent linkage of the arginine-rich fragment of the Tat protein to 1,4,7,10-tetraazacyclododecane (cyclen) results in the selective cleavage of the TAR-RNA of HIV-1 (see picture; the biotin at the 5' end acts as a label for the subsequent analysis of the cleavage fragments). The cleavage occurs at room temperature and is diminished when Eu(III) ions are present-at a concentration of about 1/10 of the concentration of the peptide-cyclen conjugate. The pH dependence indicates that two ammonium ions are responsible for the cleavage reaction. The white arrows in the schematic diagram mark the cleavage sites in RNase T1, and the black arrows the sites in the peptide-cyclen conjugate.