ANALOGS OF AMANIN

Iie 3 ‐amaninamide (3‐R) and its diastereomeric sulfoxide (3‐S) are obtained by oxidation of the bicyclic thioether peptide 2 by hydrogen peroxide in acetic acid. 2 was prepared by an intramolecular Savige‐Fontana reaction of the linear octapeptide tert.‐butylester 4 whose N ‐terminal Boc‐Hpi residue on treatment with TFA loses the Boc group and reacts under thioether formation with the released cysteine‐SH. The concomitantly deprotected carboxyl terminus is coupled intramolecularly with the free amino group of the secocompound 5 using the MA or DCCI method, thus forming the homodetic peptide ring. Compounds 3‐R and 3‐S agree very well with analog samples in chiroptical behavior. Thioether 2 and sulfoxide 3‐R exert 50% inhibition of RNA polymerase II (or B) from Drosophila melanogaster in 10– 6 M solution whereas K i of 3‐S is about five times higher.