The conversion of phthalideisoquinolines into spirobenzylisoquinolines and rhoeadine precursors

Abstract

Treatment of hydrastine with p-nitrophenylchloroformate in the presence of diethylisopropylamine resulted in opening of the isoquinoline ring with the formation of an ene-lactone carbamate. The latter compound rearranged upon treatment with methanolic sodium methoxide to an indan-1,3-dione carbamate which gave, on basic hydrolysis, the corresponding amine. This was ring closed to a spirobenzylisoquinoline. In addition, acid-catalysed dehydration of the amino indandione led to the formation of two isomeric benzazepines, synthetic precursors of the rhoeadine alkaloids. The predominately formed isomer has a substitution pattern identical with that of the rhoeadines.

Synthesis and Biosynthesis of Spirobenzylisoquinoline Alkaloids

“…This reaction (Scheme 6) has been applied to hydrastine . 43 and the intermediate dehydrophthalide b subsequently rearranged to the indandione c. The latter was hydrolysed, converted to its hydrochloride, brominated and ring closed to spiro dione d. In principle this reaction is applicable to any phthalideisoquinoline alkaloid and is potentially useful for the synthesis of the natural spirobenzylisoquinolines with two oxygens in ring C.…”