Chemical ecology deals with the chemical interactions of organisms, interactions that are pervasive at all levels of biological organization, from microbes to humans, and operate in the most diverse biological contexts. Organisms find food and seek out mates on the basis of chemicals, repel their enemies with chemicals, and fend off disease through the use of chemicals. Characterizing the molecules involved, and understanding how they function in nature is fundamental to the understanding of life itself.

 

Although a considerable number of secondary products have been identified from both animal and plant sources, few have been characterized with regard to their biological functions. Our work therefore involves close collaborations with the group of Thomas Eisner, Jacob Gould Schurman Professor of Biology at Cornell, and other leading biologists.

 

Our recent research has been concerned with the isolation and identification of biologically active compounds from insect sources. Insects are an amazingly diverse group of animals, with regard to their outward appearance as well as their ways of existing, only rivaled in beauty and sophistication by the structural diversity of their chemistry.

 

For example, recent discoveries in our labs have shown that high molecular weight secondary metabolites can play an important role in the chemical ecology of insects. Our analyses of the defensive secretions from Ladybird beetles² as well as Myrmicaria ants³ have revealed mixtures of polycyclic alkaloids derived from the oligomerization of structurally less complex precursors.  An especially interesting example is presented by the defensive chemistry of pupae of the Ladybird beetle, Epilachna borealis, which secrete a combinatorial library of macrocyclic polyamines with extremely large ring sizes, derived from the assembly of only a few simple building blocks.^4,5  Apparently, the oligomerization of relatively simple secondary metabolites can provide an important mechanism for increasing the structural diversity of defensive agents, and, most likely, other groups of bioactive natural products. 

 

Questions that guide our research in this area are: What are the functions of the secondary metabolites identified? How can individual constituents of secondary product libraries be linked to specific functions in inter- or intraspecific interactions, and are these compounds designed to match the structures of particular receptor targets? Does combinatorial assembly represent a widespread strategy in nature for generating structural diversity of secondary products, especially defensive compounds?

 

While investigations of secondary products from animal sources have traditionally relied on some form of chemical or chromatographic fractionation as a first step, the aforementioned studies have proven that the analysis of crude, unfractionated samples by NMR spectroscopy is an invaluable tool for the identification of biologically active compounds. Advanced NMR-spectroscopic techniques such as E.COSY or selective versions of three-dimensional experiments provide the means to deconvolute and characterize these complex mixtures.⁶  Whereas any analytical approach employing an initial chromatographic step, such as GC or HPLC, is likely to discriminate against some classes of components and to favor others, direct NMR-spectroscopic analyses of unfractionated samples will facilitate a more complete characterization of the biogenic material of interest. Moreover, the ability to analyze mixtures in this way opens up new perspectives towards the identification of labile metabolites, and has the potential to reveal novel classes of natural products. Consequently, NMR spectroscopic analyses play a key role in our investigations, in addition to analyses by combinations of HPLC or GC and mass spectroscopy.

 

 

1.       T. Eisner, J. Meinwald, Proc. Natl. Acad. Sci. U. S. A. 1995, 92, 1.

2.       M. Timmermans, J.-C. Braekman, D. Daloze, J. M. Pasteels, J. Merlin, J.-P. Declercq, Tetrahedron Lett. 1992, 33, 1281-1284; F. C. Schröder, T. Tolasch, Tetrahedron 1998, in press.

3.       F. Schröder, H. Baumann, M. Kaib, V. Sinnwell, Chem. Commun. 1996, 2139-2140; F. Schröder, S. Franke, W. Francke, H. Baumann, M. Kaib, J. M. Pasteels, D. Daloze, Tetrahedron 1996, 52, 13539-13546; F. Schröder, V. Sinnwell,
H. Baumann, M. Kaib, W. Francke, Angew. Chem. Int. Ed. 1997, 36, 77-80.

4.       F. C. Schröder, J. J. Farmer, A. B. Attygalle, S. R. Smedley, T. Eisner, and J. Meinwald, Science 1998, 281, 428-431.

5.       F. C. Schröder, J. J. Farmer, S. R. Smedley, T. Eisner, and J. Meinwald, Tetrahedron Lett. 1998, 39, 6625-6628; F. C. Schroeder, S. R. Smedley, L. K. Gibbons, J. J. Farmer, A. B. Attygalle, T. Eisner, J. Meinwald, Proc. Acad. Natl. Sci. USA 1998, 95, 13387-13391; F. C. Schroeder, J. J. Farmer, A. B. Attygalle, S. R. Smedley, T. Eisner, and J. Meinwald, J. Am. Chem. Soc. submitted.

6.       C. Zwahlen, S. J. F. Vincent, G. Bodenhausen, Angew. Chem.Int. Ed. Engl. 1992, 31, 1248-1251; M. Eberstadt, G. Gemmecker, D. F. Mierke, H. Kessler, Angew. Chem. Int. Ed. Engl. 1995, 34, 1995, 1671-95.