Synthesis of isotope labeled N-acyl-L-homoserine lactones (AHLs)

Dorota Jakubczyk

Institute of Functional Interfaces (IFG)

Karlsruhe Institute of Technology (KIT)

Hermann von Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany

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

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).

Fig.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.²

In contrary to the most of isotopic labeling methods based on the use of deuterium or tritium gas,³ this procedure does not require sophisticated apparatuses and complicated work-up.

References:

[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] Schwarzmann, G. Biochim. Biophys. Acta 1978, 529, 106

[3] Kaplan, H. B.; Eberhard, A.; Widrig, C.; Greenberg, E. P. J. Labelled Comp. Radiopharm. 1985, 22, 387.