Acronycine oxidation

A 1,4-dioxepin fused derivative 122 of the anticancer agent acronycine was prepared by lead tetraacetate oxidation of c/.s-l,3-dihydroxy-l,2-dihydroacronycine followed by treatment with sodium borohydride <00NPL183>. 

Baeyer-Villiger oxidation of the anti-tumour alkaloid acronycine and its 2-nitro derivative, led to the chromeno[5,6-b][4,l]benzoxazepin-8-one 144 (R = H) and 144 (R = NO2) respectively <00NPL183>. 

Racemic cii-diols 48. and were prepared as previously described by catalytic osmic oxidation of acronycine (IJ and 6-demethoxyacronycine (17 ). respectively. Treatment of those diols with excess acetic anhydride afforded the corresponding diesters 6 and 67., respectively. When only one equivalent of anhydride was used, monoesters at the less hindered 2-position, such as acetate and benzoate 69. were obtained. Treatment of the monobenzoate 69, with excess acetic anhydride furnished the mixed ester JR-... 

Acronycine was isolated from the bark of the Australian scrub ash, Baurella simplicifolia =Acronychia baueri) (Rutaceae), together with related alkaloids [1]. Acronycine is classified as an acridone alkaloid, and acridone is an oxidized derivative of acridine. Acridine itself was isolated from coal tar in the nineteenth century, but the isolation of acronycine and related alkaloids was the first occasion that the acridine (acridone) unit was isolated from a higher plant. 

In addition, oxidation reactions performed on pyranoacridones led to several alkaloids modified on the C and D rings, and to acronycine analogues with improved antitumor activity. 

Racemic trans-l,2-dihydro-l,2-dihydn>xyacronycine (158) was first obtained in very low yield by oxidation of acronydne (2) with chromium trioxide in acetic add followed by alkaline hydrolysis of the intomediate troru-diol monoacetate 274). A more convenient access was recently described 371), based on a previous shufy of the oxidation of acronydne by potassium permanganate 372). Thus, treatment of acronycine (2) with potassium permanganate in aqueous acetone gave l-oxo-2-hydroxy-l,2-dihydroacronydne (376) in 31% yield, accompanied by smaller amounts of c -l,2-dihydro-l,2-dihydroxyacronydne (157) and of the acetone adduct 377. Sodium borohydride reduction of l-oxo-2-hydroxy-... 

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