head of the department: Prof. Kalesse

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Recent Submissions

  • Total Synthesis of Nannocystin Ax.

    Poock, Caroline; Kalesse, Markus; Hemholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-09-01)
    The total synthesis of nannocystin Ax in an overall yield of 11% with 14 steps as the longest linear sequence is reported. Nannocystin Ax is a cytotoxic 21-membered depsipeptide and was isolated from the myxobacterial genus Nannocystis sp. The synthesis uses a vinylogous Horner-Wadsworth-Emmons reaction (HWE) and a vinylogous Mukaiyama aldol reaction (VMAR) as the key steps for the construction of the polyketide fragment. The macrocycle was closed via a macrolactamization reaction using COMU.
  • RNA polymerase motions during promoter melting.

    Feklistov, Andrey; Bae, Brian; Hauver, Jesse; Lass-Napiorkowska, Agnieszka; Kalesse, Markus; Glaus, Florian; Altmann, Karl-Heinz; Heyduk, Tomasz; Landick, Robert; Darst, Seth A; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-05-26)
    All cellular RNA polymerases (RNAPs), from those of bacteria to those of man, possess a clamp that can open and close, and it has been assumed that the open RNAP separates promoter DNA strands and then closes to establish a tight grip on the DNA template. Here, we resolve successive motions of the initiating bacterial RNAP by studying real-time signatures of fluorescent reporters placed on RNAP and DNA in the presence of ligands locking the clamp in distinct conformations. We report evidence for an unexpected and obligatory step early in the initiation involving a transient clamp closure as a prerequisite for DNA melting. We also present a 2.6-angstrom crystal structure of a late-initiation intermediate harboring a rotationally unconstrained downstream DNA duplex within the open RNAP active site cleft. Our findings explain how RNAP thermal motions control the promoter search and drive DNA melting in the absence of external energy sources.
  • A simple and efficient method for the preparation of 5-hydroxy-3-acyltetramic acids.

    Trenner, Johanna; Prusov, Evgeny V; Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany. (2015)
    Oxidation of the bisenolates of 3-acyltetramic acid to the corresponding 5-hydroxylated compounds using molecular oxygen is reported. The deprotection of the resulting compounds was also achieved.
  • Synthesis of the spiroketal core of integramycin.

    Prusov, Evgeny V; Department of Medicinal Chemistry, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany (2013)
    A concise synthetic strategy towards the spiroketal core of the HIV-integrase inhibitor integramycin (1) was developed. The required ketone precursor was efficiently constructed from two simple and easily accessible subunits by means of a hydrozirconation/copper catalyzed acylation reaction. The effects of different protecting groups on the spiroketalization step were also investigated.
  • Total synthesis of antibiotics: recent achievements, limitations, and perspectives.

    Prusov, Evgeny V; Helmholtz Zentrum für Infektionsforschung, Braunschweig, Germany. (2013-04)
    Several recently accomplished total syntheses of antibiotic natural products were summarized in this review in order to present current trends in this area of research. Compounds from different substance classes, including polyketide, depsipeptide, polyketide-polypeptide hybrid, and saccharide, were chosen to demonstrate the advancement in both chemical methodology and corresponding synthetic strategy.
  • Mode of action of epoxyphomalins A and B and characterization of related metabolites from the marine-derived fungus Paraconiothyrium sp.

    Mohamed, Ietidal E; Kehraus, Stefan; Krick, Anja; König, Gabriele M; Kelter, Gerhard; Maier, Armin; Fiebig, Heinz-Herbert; Kalesse, Markus; Malek, Nisar P; Gross, Harald; Department of Botany, University of Khartoum, Khartoum, Sudan. (2010-12-27)
    Epoxyphomalins A (1) and B (2) are highly potent cytotoxic fungal metabolites. During the course of purifying larger quantities of 1 and 2 from Paraconiothyrium sp. fermentation extracts, three new epoxyphomalins (3-5) were isolated and characterized, showing modifications to the oxidation pattern of the cyclohexene moiety or of C-9 of the decalin system. IC(50) values for cytotoxicity against a panel of 36 human tumor cell lines were determined for all new compounds. Compound 4 was found to be cytotoxic particularly toward prostate PC3M (IC(50) = 0.72 μM) and bladder BXF 1218 L (IC(50) = 1.43 μM) cancer cell lines. In addition, inhibition of chymotrypsin-, caspase-, and trypsin-like activity of purified 20S proteasomes was determined for epoxyphomalins A (1) and B (2). The results indicate that compounds 1 and 2 exert their cytotoxic effect through potent inhibition of the 20S proteasome.
  • Stereoselective total synthesis of etnangien and etnangien methyl ester.

    Li, Pengfei; Li, Jun; Arikan, Fatih; Ahlbrecht, Wiebke; Dieckmann, Michael; Menche, Dirk; Institut für Organische Chemie, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany. (2010-04-16)
    A highly stereoselective joint total synthesis of the potent polyketide macrolide antibiotics etnangien and etnangien methyl ester was accomplished by a convergent strategy and proceeds in 23 steps (longest linear sequence). Notable synthetic features include a sequence of highly stereoselective substrate-controlled aldol reactions to set the characteristic assembly of methyl- and hydroxyl-bearing stereogenic centers of the propionate portions, an efficient diastereoselective Heck macrocyclization of a deliberately conformationally biased precursor, and a late-stage introduction of the labile side chain by means of a high-yielding Stille coupling of protective-group-free precursors. Along the way, an improved, reliable protocol for a Z-selective Stork-Zhao-Wittig olefination of aldehydes was developed, and an effective protocol for a 1,3-syn reduction of sterically particularly hindered beta-hydroxy ketones was devised. Within the synthetic campaign, a more detailed understanding of the intrinsic isomerization pathways of these labile natural products was elaborated. The expedient and flexible strategy of the etnangiens should be amenable to designed analogues of these RNA-polymerase inhibitors, thus enabling further exploration of the promising biological potential of these macrolide antibiotics.
  • Thiourea-catalyzed direct reductive amination of aldehydes

    Menche, Dirk; Arikan, Fatih (Thieme, 2007-09-25)
  • Synthesis of the northern hemisphere of amphidinolide H2

    Liesener, F.P.; Jannsen, U.; Kalesse, M. (Thieme, 2006)