THE FOLDED CONFORMATION-THE RESULT OF PI-PI-INTERACTIONS? Michael Bolte, Institut fuer Organische Chemie Johann-Wolfgang-Goethe-Universitaet Marie-Curie-Str.11 60439 Frankfurt am Main Germany

The so-called folded conformation by which an aromatic ring shields a heterocycle is a well known phenomenon. It was first discoverd by NMR (Kopple & Marr, 1967) and later on by X-ray crystallography (e.g. Lin & Webb, 1973) for diketopiperazines. But it can also be found for hydantoines (Fujiwara, Bose, Manhas & van der Veen, 1979), 1,4-dihydorpyridines (Iwasaki, Watanabe & Maeda, 1987) and dihydrooxazinones (Bolte, 1995).

We have determined the crystal structures of several bis-lactim ethers, which are important intermediates of a synthetic route to enantiomerically pure amino acids (Schoellkopf, 1983).

Some bis-lactim ethers with aromatic side chains, for which the folded conformation was expected, show this conformation while others do not.

Since the understanding whether a small organic molecule adopts the folded conformation could also be very helpful for the conformational analysis of biomacromolecules like proteins it is necessary to know the reasons for the appearance of this conformation. The careful and attentive inspection of all these crystal structures leads to the conclusion that the main reason whether a molecule adopts the folded conformation are steric interactions. We do not deny that there are attractive pi-pi-interactions between heterocycle and aromatic residue, but more important, and decisive, are steric forces.

References: Bolte. M., (1995). Acta Crystallogr. C51, 2587-2593. Fujiwara, H., Bose, A.K., Manhas, M.S. & van der Veen, J.M. (1979). J. Cem. Soc. Perkin Trans. 2, pp. 653-658. Iwasaki, F., Watanabe, T. & Maeda K. (1987). Bull. chem. Soc. Jpn, 60, 1255-1259. Kopple, K.D. & Marr, D.H. (1967). J. Am. Chem. Soc. 89, 6193-6200. Lin, C.-F., & Webb, L.E. (1973). J. Am. Chem. Soc. 95, 6803-6811. Schoellkopf, U., (1983). Top. Curr. Chem. A109, 65-83.