SYNTHESIS OF AZABENZISOCHROMANEQUINONE ANTIBIOTICS .2. 9(6)-HYDROXY-6(9)-AZABENZISOCHROMANEQUINONES VIA AMINOISOCHROMANES AND MELDRUM ACID

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