Total Synthesis of Mimosamycin

The synthesis of mimosamycin has been achieved in 6 steps starting from 7-hydroxy-6-methylisoquinoline (7). Copper-catalyzed autoxidation of 7, which was prepared in 80% over-all yield in 5 steps from 3-methoxy-4-methylbenzaldehyde, gave 6-methyl-3, 5-dimorpholino-7, 8-dioxo-7, 8-dihydroisoquinoline (8a). Upon treatment with sulfuric acid-methanol followed by diazomethane, the o-quinone (8a) was converted to 7-methoxy-6-methyl-3-morpholino-5, 8-dioxo-5, 8-dihydroisoquinoline (10a). Reductive acetylation of 10a with zinc-acetic acid and acetic anhydride gave 5, 8-diacetoxy-7-methoxy-6-methyl-3-morpholinoisoquinoline, which was quaternized at the isoquinoline nitrogen with methyl iodide. Treatment of the methiodide (12a) with silver oxide gave rise to in one-step 7-methoxy-2, 6-dimethyl-3, 5, 8-trioxo-2, 3, 5, 8-tetrahydroisoquinoline, which was identified with a specimen of natural mimosamycin isolated from the culture filtrate of Streptomyces lavendulae No. 314.