SYNTHESIS OF BILIVERDINS WITH STABLE EXTENDED CONFORMATIONS .1.

Biliverdins with extended conformations stabilized by intramolecular e thyl bridges were obtained by base treatment of helical biliverdins wi th 2-chloroethyl side chains. Thus, neobiliverdin IX beta (6) was obta ined by reaction of 13,18-di-(2-chloroethyl)-biliverdin 5 with DBU. Du ring the reaction the 2-chloroethyl-C(13) residue underwent an inaamol ecular substitution reaction with N-24 while the 2-chloroethyl-C(18) r esidue underwent an elimination reaction to form a vinyl residue. This reaction scheme was unambiguously demonstrated by performing the synt hesis of [N-15-24]-dihydro-neobiliverdin IX beta (19) and of [N-15-23] -dihydrophorcabilin (31). The method was then applied to the synthesis of neobiliverdin IX delta, a natural product isolated from the ovarie s of the sea snake Turbo cornutus. It was concluded that when the 2-ch loroethyl side chains are at C(3) (or the equivalent C(17)) and C(2) ( or the equivalent C(18)) positions of the biliverdin, elimination reac tions lead to vinyl residues in basic media; at any other of the beta- pyrrole sites, treatment with base leads to the formation of seven-mem bered rings by intramolecular substitution reactions.