Synthesis of biliverdin IXγ (pterobilin)

Abstract

Condensation of a bis(acetoxyethyl)pyrromethane dicarboxylic acid ( 11d) with a diformylpyrro-ketone ( 12b) afforded a bis(acetoxyethyl)-γ- meso-hydroxyporphyrin ( 13d) which was converted into the related bis(chloroethyl)-γ-benzoyloxyporphyrin ( 14f). The Zn complex of the latter was transformed by brief treatment with base, followed by chloromethylethyl ether into the zinc bis(chloroethyl)-γ-ethoxy-methoxyporphyrin ( 20b). Dehydrochlorination with potassium t-butoxide in t-butanol, and acid catalysed demetallation and deprotection then afforded the somewhat unstable blue γ-oxyprotoporphyrin dimethyl ester ( 21). The Fe-complex of the latter readily underwent oxidative ring opening by aerial oxidation in pyridine, and after demetallation gave biliverdin IXγ (pterobilin) dimethyl ester ( 22).