Isolierung und Strukturermittlung der neuen Cyclosporine E, F, G, H und I

Abstract

Isolation and Structure Determination of the New Cyclosporins E, F, G, H und I The cyclosporins, a new group of biologically active metabolites, are produced by the fungus Tolypocladium inflatum GAMS (formerly designated as Trichoderma polysporum [LINK EX PERS.] RIFAI). They represent neutral cyclic oligopeptides composed of 11 amino acids. In addition to the already described cyclosporins A–D new minor compounds, cyclosporins E–I, have now been isolated from the crude cyclosporin‐complex by applying extensive chromatographical separation procedures. The structures of the new compounds have been determined by spectroscopical evidence, hydrolytic cleavage and chemical correlation reactions as well as by X‐ray analysis of suitable derivatives. Cyclosporins A, B, C, D and G differ from each other only in the nature of the amino acid no. 2. Cyclosporins E and I are N ‐demethylated congeners of cyclosporins A and D respectively, Cyclosporin F has been recognized as deoxycyclosporin A, whereas Cyclosporin H represents an epimeric form of cyclosporin A and contains N ‐methyl‐D‐valine in position 11.