Synthesis of Biliverdins with Stable Extended Conformations. Part I.

ITURRASPE, JOSÉ B.I.; BARI, SARA E.; FRYDMAN, JAIME BENJAMÍN

TETRAHEDRON

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 1995 vol. 51 p. 2243 - 2254

0040-4020

Biliverdins with extended conformations stabilized by intramoleeular ethyl bridges wereobtained by base treatment of helical biliverdins with 2-chloroethyl side chains. Thus, neobiliverdin IX beta (6) was obtained by reaction of 13,18.di-(2-chloroethyl)-biliverdin$ with DBU. During the reaction the 2-ehloroethyI-C(13) residue underwent an intramolecular substitution reaction with N-24 while the 2- chloroethyl-C(18) residue underwent an elimination reaction to form a vinyl residue. This reaction scheme was unambiguously demonstrated by performing the synthesis of [15N-24]-dihydro-nenbiliverdin IX beta (19) and of [15N-231-dihydrophorcabilin (31). The method was then applied to the synthesis of neobiliverdin IX gamma, a natural product isolated from the ovaries of the sea snake Turbo cornutus. It was concluded that when the 2-ehloroethyl side chains are at C(3) (or the equivalent C(17)) and C(2) (or the equivalent C(18)) positions of the biliverdin, elimination reactions lead to vinyl residues in basic media; at any other of the 13-pyrrole sites, treatment with base leads to the formation of seven-membered rings by intramolecular substitution reactions