Occurrence of cyclosporins and cyclosporin-like peptolides in fungi

Apart from 17 previously listed fungal taxa producing cyclosporin A and its natural congeners B to Z, several additional and taxonomically diverse strains producing the single novel component [Thr2,Leu%Leul~ or cyclosporin-iike peptolides (eg SDZ 214-103 = [Thr2,LeuS,D-HivS,Leul~ have recently been described. We report here the isolation of two further and novel cyclosporins, [Thr2,Leu%Alal~ (2J and [Thr2,11eS]cyclosporin (3), from strains classified as Acremonium luzulae (Fuckel) W Gams and Leptostroma anamorph of Hypoderma eucalyptii Cooke & Harkn, respectively, in both new strains the usual pattern of cyclosporins A to Z is not found. The structure elucidations of 2 and 3 are based on NMR spectroscopy, and biological data (immunosuppressive activity, cyclophilin-binding affinity and antifungal effects) are presented.