Synthesis of azabenzisochromanequinone antibiotics .2. 9(6)-hydroxy-6(9)-azabenzisochromanequinones via aminoisochromanes and Meldrum's acid

摘要

The synthesis of 6(7)-amino-5,8-dimethoxyisochromanes 7,8, pre cursors of the B-C ring system of benzisochromanequinone antibiotics 1, is described. Subsequent N-alkylation using Meldrum's acid/trimethyl orthoformate followed by a high temperature cyclization and oxidative demethylation yields 9(6)-O-demethyl- 6(9)azaeleutherins 13 and 6(9)-azaepinanaomycin A methyl esters 14. The novel aza-analogues allowed further studies on the structure-activity relations in the field of (aza)benzisochromanequinone antibiotics.