7.8- Dioxygenated isoquinolines

In the third example, the Reissert reaction88 was used by Jackson and Stewart74 to prepare still another l-benzyl-7,8-dioxygenated isoquinoline [Eq. (41)]. The application of a Reissert reaction to a SchifF... 

A synthesis of 7,8-dioxygenated isoquinolines (found in cularine alkaloids) requires o-metallation of the Af-protected -phenylethylamine. The primary amine is protected by reaction with two equivalents of trimethylsilyl chloride. Phenylhydroxylamine and the allenic nitrile (53.7) react in boiling ethanol over 48 h to give a high yield of 4-aminoquinoline—an important intermediate for the synthesis of some antimalarial drugs. 

A source of the polyketide 9 was the protected equivalent 16 (ref. 13) which can be obtained by ozonolysis of the diene 15 (Scheme 2). Exposure of 16 to silica gel affords phenol 17 which serves as a precursor to a 6,8-dioxygenated isoquinoline. Methylation followed by condensation with ammonia gives isoquinoline 18 from which the isoquinoline 14 can be secured by selective cleavage of the hydroxyethyl group. 

The phenethylisoquinoline homopetaline which possesses the unusual 7,8-dioxygenation pattern in the isoquinoline moeity, has been synthesized along classical lines, utilizing a bromine blocking group to direct the Bischler-Napieralski cyclization. ... 

The two Dolichothele species, D. longimamma and D. uberiformis, contain simple isoquinolines that are monooxygenated in the 6- or 8-position. Probably, these compounds are biosynthesized by cyclisation of meta-tyidimnes. In D. uberiformis a 5,7-dioxygenated compound, uberine, was also found (Ranieri and McLaughlin 1976, 1977). 

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