9-Hydroxy-2-methyl ellipticine

NaH, dimethylformamide (DMF), CH3I], undergoes electrophilic nitration (89), Friedel-Crafts acylation (90), and alkylation (91) at the C-9 position. Although attempts to effeet a Baeyer-Villiger oxidation of ketone 90 were successful, the route was laborious since oxidation to amine oxide 92 preceded oxidation of the methyl ketone 90. However, a Dakin reaction of aldehyde 91 gave 9-hydroxy-6-methylellipticine (93) in excellent yield. It remains to be seen if this methodology can be extended to an N-unsubstituted ellipticine. 

Paoletti, C., LePecq, J. B., Dat-Xuong, N., et al.. Antitumor activity, pharmacology and toxicity of ellipticines, ellipticinium and 9-hydroxy derivatives preliminary clinical trials of o-methyl-9-hydroxy ellipticinium 9NSC 264-137, Recent Results Cancer Res. (1980) 74, 107-124. 

Ellipticine (E) 1 is an indolic alkaloid with antitumor activity. Some of its phenolic derivatives as N-methyl-9-hydroxyellipticine (Celiptinium), obtained from 9-hydroxy ellipticine (9-OH E), exhibit high cytotoxicity. 38 Syntheses of 9-OH E are not satisfactory considering yields and cost, justifying the attempts at the direct conversion of E to 9-OH E via 9-oxoellipticine (9-0X0 E). Potassium nitrosodisulfonate (Fremy s salt), a valuable oxidant for the synthesis of quinone-imine from heterocyclic amines,139 was used. Under these conditions the conversion of E to 9-0X0 E was observed for the first time. Its reduction to 9-OH E is then easily achieved with ascorbic acid. The radical nature of Fremy s salt [ 0-N(S03K)2] led us to carry out the oxidation reaction under sonication in order to increase the yields via an easier electron transfer.1 1... 

Zwelling LA, Michaels S, Kerrigan D, Pommier Y et al. 1982 Protein-associated deoxyribonucleic acid strand breaks produced in mouse leukemia LI210 cells by ellipticine and 2-methyl-O-hydroxy- ellipticinium. Biochem Pharmacol 31 3261-3267... 

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