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The spatial conformation of the “polar” form of enniatin B has been established. A conformation of the N1 type has been proposed for the “nonpolar” form.

Molecular orbital calculations using the PCILO method are performed on the conformation of the symmetrical form of enniatin B. The values of the Φ and ψ angles found for the preferred conformation agree closely with the results of X-ray study of the K + complex of enniatin B.

Detailed CD- and UV-studies indicate a conformational change in antamanide by interaction with cations or polar solvents. The conformation formed on addition of water is similar to that of the complex. A model for antamanide already suggested by Ovchinnikov's (1) group is confirmed by CD-data and by substitutions in position 1 and 4 (2). The unusually high negative dichroism at about 230 nm is ascribed to n → π ∗ transitions of transoid tertiary amide groups distorted out of plane. Non planar amides probably also determine the dichroic properties of enniatin B (3) and of some acetylproline derivatives (4).

THE interaction of a biologically active substance with a selective receptor (for instance, substrate and enzyme) to cause a certain physiological effect is chemically complex, requiring not only a certain minimum of steric congruity of the molecules but also a given electron density distribution in the interacting functional centres. If either of these requirements is not satisfied, the reaction will either not take place at all or its effectiveness will be diminished by several orders of magnitude. It is thus important to discover the limits of steric and electronic matching, both in the rational search for substances with similar, modified or antagonistic action, and to understand the underlying mechanism.

Publisher Summary This chapter discusses the structure of and microbiological activity in the Enniatin-series. The cyclic depsipeptide is built up by regularly alternating D-α-hydroxyisovaleric acid and a N-methyl-amino-acid, which in Enniatin A is N-methyl- L-isoleucine and in Enniatin B N-methyl- L-valine. The tertiary butyl ester of D-α-hydroxy-isovaleric acid is coupled by means of benzene sulfochloride to the corresponding benzyloxycarbonyl-amino-acid in the presence of pyridine. By enlarging the decarbobenzoxylated tetradepsipeptide ester used in the Enniatin B synthesis with the didepsipeptide acid containing L-valine, the hexadepsipeptide for the monodesmethyl-product can be obtained. The synthetic route to the tridesmethyl-enniatin B resembles the one used for the synthesis of the Enniatin B, differing only by the use of L-valine instead of N-methyl- L-valine.

The present state of the chemistry of the valinomycin type and enniatin B type depsipeptide ionophores is reviewed. An analysis is carried out on the relation between the primary structure, the conformation, the complexing properties, and the membrane activity of valinomycin and its numerous analogs. The correlations resulting from such a study have made it possible to carry out the predetermined synthesis of valinomycin analogs excelling the parent compound in complexing properties.

Judging by the physical and chemical properties and “bacterial spectra”, the antibiotic substance, Enniatin, previously isolated from a strain ofFusarium by the authors, appears to be identical with that which was recently reported byCook et al. derived from another strain and designated by them as Lateritiin-I, although the reported empirical formulae differ. Numerous physical and chemical characteristics of Enniatin and its degradation products are given, and, further, two relatedFusarium antibiotics, here designated as Enniatin B and C, are briefly described.

Die Struktur von Enniatin B, eines antimikrobiellen Wirkstoffes aus Fusarienstammen (ETH, Zurich), wird durch Synthese als die eines Cyclohexapeptolids bewiesen (vgl. X).