Synthesis
of isotope labeled N-acyl-L-homoserine lactone (AHL) derivatives
Dorota Jakubczyk
Karlsruhe Institute of
Technology (KIT)
Institute of Functional
Interfaces (IFG)
North Campus / Hermann von
Helmholtz-Platz 1,Building 330
76344 Eggenstein-Leopoldshafen,
Germany
email: dorota.jakubczyk@kit.edu
N-acyl-L-homoserine lactones (AHLs) are natural products produced by
bacteria such as Pseudomonas aeruginosa and constitute so-called quorum sensing
molecules. Such molecules mediate a cell-to-cell signalling. This inter-bacterial
communication causes for example biofilm formation and
thus contributes to virulence. Moreover AHL interacts with a variety of
mammalian cells (inter-kingdom signalling), what e.g. effects in induction of
the chemotaxis of neutrophils.1-3
We are interested in the synthesis of the deuterium and tritium labeled
AHLs which can help to resolve the mechanism of the N-acyl-L-homoserine lactone crossing through eukaryotic cell membranes and its
distribution within the cell.
Therefore we present
herein the novel method of deuterium and tritium labeling of terminally
unsaturated AHLs via catalytic reduction of the double bond (see Figure 1).
Figure 1. a) Pd(OAc)2, CH3COOH, MeOH, THF, NaB[nH4],
NaOH, MeOH, -196°C-RT; b) HClO4,
CH2Cl2, 0°C-RT; n=2 or 3.
This uncommon reduction of the
double bond using sodium borohydride-[2H]
or sodium borohydride-[3H] was performed
in the presence of palladium(II) acetate as a catalyst in the liquid nitrogen.4
In contrary to the
most of isotopic labeling methods based on the use of deuterium or tritium gas,5
this procedure does not require sophisticated apparatuses and complicated
work-up.
[1] Amara, N.; Mashiach, R.; Amar, D.; Krief,
P.; Spieser, S. A. H.; Bottomley,
M. J.; Aharoni, A.; Meijler,
M. M. J. Am. Chem. Soc. 2009, 131, 10610.
[2] Boyer, M.;
Wisniewski-Dye, F. FEMS Microbiol. Ecol. 2009, 70, 1.
[3] Ritchie, A. J.; Jansson, A.; Stallberg, J.;
Nilsson, P.; Lysaght, P.; Cooley, M. A. Infect.
Immun. 2005, 73, 1648.
[4] Schwarzmann, G. Biochim. Biophys. Acta 1978, 529, 106.
[5] Kaplan, H. B.;
Eberhard, A.; Widrig, C.; Greenberg, E. P. J. Labelled Comp. Radiopharm. 1985, 22, 387.