Background: Cell to cell signaling systems in Gram-negative bacteria rely on small diffusible molecules such as the N-acylhomoserine lactones (AHL). These compounds are involved in the production of antibiotics, exoenzymes, virulence factors and biofilm formation. They belong to the class of furanone derivatives which are frequently found in nature as pheromones, flavor compounds or secondary metabolites. To obtain more information on the relation between molecular structure and quorum sensing, we tested a variety of natural and chemically synthesized furanones for their ability to interfere with the quorum sensing mechanism using a quantitative bioassay with Chromobacterium violaceum CV026 for antagonistic and agonistic action. We were looking at the following questions:

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[reaction: see text] An enantiospecific synthesis of the AB fragment of lactonamycin (5) is achieved in eight steps from dimethyl D-tartrate. Ester enolate chemistry features prominently in the sequence.

A synthetic route to a class of substituted butenolides isolated from Streptomyces antibioticus has been elaborated. The process involves coupling of the readily available menthylated furanone 5 with aldehydes.

Analogs of naturally occurring furanones that were reported to be weak inhibitors of Serratia marcescens chitinases were prepared and tested towards various chitinases. Some of these compounds -but not the natural products -were found to be weak but selective inhibitors; all glycosylated analogs tested were inactive. Activation of the plant enzyme hevamine was observed in one case, which is unusual.The polysaccharide chitin is depolymerized in nature by chitinases [EC 3.2.1.14] belonging to the glycosidase families 18 and 19. 1 Family 18 chitinases are widely distributed in mammals, arthropods, nematodes, protozoa, plants, fungi, bacteria, and viruses, whereas family 19 chitinases only occur in plants and in addition also in Streptomyces. Besides their role as digestive enzymes and as defense mechanisms, chitinases play important roles in the regulation of growth and development of many organisms (for a review, see ref. 2 ).Selective inhibition of chitinases is an attractive target for the development of antifungal agents, parasiticides, and insecticides for agricultural and medical applications. Up to now, the most potent inhibitor of chitinases is allosamidin (1), which shows remarkable species selectivity, as revealed by IC 50 values ranging from 0.0002 mM to 20.9 mM (for a review, see 3 ). The recent finding of a cyclic peptide as a potent inhibitor 4 demonstrates that quite different chemical compounds might be suited as chitinase inhibitors, but both allosamidin (1) and this peptide are too complicated to allow a large-scale synthesis and in addition, at least allosamidin (1) is unstable under field conditions. The design of new chitinase inhibitors avoiding these problems is therefore a challenge.We present here compounds (Figure 1, Scheme 2) that were synthesized after finding that the butenolides 2a and 3a, which were isolated from the fermentation broth of Streptomyces antibioticus TÜ 99, showed some activity as inhibitors of the chitinase of Serratia marcescens in preliminary tests. 5