4th EucheMs chemistry congress

Poster Session 2
s1364
chem. Listy 106, s257–s1425 (2012)
Poster session 2 - organic chemistry
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reCent AdvAnCeS towArdS the SyntheSiS of
ruBroMyCinS
M. wiLSdorf 1 , h. reiSSiG 1
1 Freie Universität Berlin, Institut für Chemie und Biochemie,
Berlin, Germany
The rubromycin family is a class of natural products which
is known for exhibiting antibiotic, cytostatic and antimicrobial
activity. This type of natural products is characterized by a
challenging molecular architecture whose basic structure consists
of a highly functionalized naphthoquinone moiety which is linked
[1, 2]
to an isocoumarin unit by a 5,6-spiroketal core.
In continuation of our long standing interest in the synthesis
of rubromycin and heliquinomycin we here describe our recent
results concerning a) the improved synthesis of model substrates,
b) new insights into the process of the acid promoted ketalization
of benzannuated precursors and c) the challenges and problems
[3, 4]
which still have to be solved.
references:
1. Review: M. Brasholz, S. Sörgel, C. Azap, H.-U. Reissig
Eur. J. Org. Chem. 2007, 3801–3814.
2. M. Chino, K. Nishikawa, T. Tsuchida, R. Sawa,
H. Nakamura, K. Nakamura, Y. Muraoka, D. Ikeda,
H. Naganawa, T. Sawa, T. Takeuchi, J. Antibiot. 1997, 50,
143–146.
3. S. Sörgel, C. Azap, H.-U. Reissig Org. Lett. 2006,
4875–4878.
4. C. Venkatesh, H.-U. Reissig Synlett 2008, 3605–3614.
Keywords: Natural products;
4 th EucheMs chemistry congress
P - 1 0 0 6
A CheMiCAL SyntheSiS of dAnSyLAted
udP-MurnAC-PentAPePtidefor hiGh
throuGhPut MrAy ASSAyS
S. wohniG 1 , C. duCho 1
1 University of Paderborn, Chemistry, Paderborn, Germany
Because of the increase in bacterial resistance, the discovery
of new antibiotics is of high relevance. The membrane-associated
enzyme MraY, which catalyses the transfer of a
glycosylphosphate-pentapeptide moiety onto a lipophilic
membrane anchor in the course of bacterial peptidoglycan
formation, represents an attractive target for the development of
new antibacterial agents [1,2] . This enzyme is inhibited by the
naturally occurring muraymycin nucleoside lipopeptide
antibiotics [3] . The fluorescently labelled MraY substrate is required
for high throughput MraY assays as reported by Stachyra et al.,
who used the dansylated derivative of UDP-MurNAcpentapeptide
for an in vitro MraY assay [4] . A chemical synthesis
of dansylated UDP-MurNAc-pentapeptide is desired in order to
obtain an adequate amount, while the isolation from bacteria and
subsequent dansylation of UDP-MurNAc-pentapeptide affords
only a small amount of the desired product.
Starting from commercially available N-acetylglucosamine,
a protected glycosylphosphate precursor was prepared over seven
steps in an overall yield of 30%. The peptide unit was synthesised
using Cbz-protection of the amino function and different peptide
coupling procedures. A novel convergent [4+1]-strategy for
pentapeptide assembly gave the dansylated glycosylphosphate-
-pentapeptide. Following debenzylation and diphosphate coupling
with a reactive uridine derivative, the target compound was
obtained after final global deprotection. Latest results on this
synthetic approach will be presented.
references:
1. K. I. Kimura, T. D. H. Bugg, Nat. Prod. Rep. 2003, 20,
252-273.
2. M. Winn, R. J. M. Goss, K. I. Kimura, T. D. H. Bugg,
Nat. Prod. Rep. 2010, 27, 279-304.
3. L. A. McDonald, L. R. Barbieri, G. T. Carter, E. Lenoy,
J. Lotvin, P. J. Petersen, M. M. Siegel, G. Singh, R. T.
Williamson, J. Am. Chem. Soc. 2002, 124, 10260-10261.
4. T. Stachyra, P. Ferari, A. Bouhss, J. van Heijenoort,
D. Mengin-Lecreulx, D. Blanot, J. Bilton, D. LeBeller,
Antimicrob. Agents Chemother. 2004, 48, 897-902.
Keywords: Antibiotics; Carbohydrates; Fluorescence;
Nucleotides; Peptides;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc