Analogs of phalloidin

The analogs [D‐Abu2‐Lys7]‐phalloin (1) and [D‐Ala2‐Leu7]‐phalloin (2) are obtained by cyclization of the monocyclic thioether peptides 5 and 7 with DCCI and diphenylphosphoro‐azidate respectively. For the synthesis of 5 and 7 an intramolecular Savige‐Fontana reaction of the linear heptapeptide tert.‐butylesters 4 and 6 is applied. On treatment in dilute solution with TFA the classically synthesized peptides 4 and 6 lose their N‐terminal Boc groups thus giving rise to the reaction of the Hpi residues with the released cysteine SH‐groups. The lysine analog 1 binds to F‐actin with an association constant of 1.3 times 10‐6M whereas analog 2 exhibits practically no affinity. By reaction of 1 with tetramethyl‐rhodaminyl‐isothiocyanate a fluorescent derivative, rhoda‐minyl‐lysine‐phallotoxin (RLP), is obtained as a novel fluorescent probe for the visualization of F‐actin in cell preparations.