The regional selective hydrolysis or hydrolytic oxidization of indolo[3,2-b]quinolinium salts: a new simple synthetic approach to substituted indolo[3,2-b]quinolinones

Abstract

In this article, the regioselective hydrolysis or hydrolytic oxidation of indolo[3,2-b]quinolinium salts was examined, which lead to the formation of indolo [3,2-b]quinolinone as the major product or the sole product in different conditions. This work provided a new method for the preparation of substituted indolo [3,2-b]quinolinones. Keywords: Indolo[3,2-b]quinolinium salt, indolo[3,2-b]quinolinone, hydrolysis, hydrolytic oxidation IntroductionIndolo [3,2-b]quinolines 1 and indolo [3,2-b]quinolinones 2 are sometimes referred in the literature to as quindolines and quindolinone, respectively. (Figure 1) A number of indolo [3,2-b]quinoline and indolo [3,2-b]quinolinone alkaloids, such as quindoline 1, 1,2 quindolinone 2, 3 cryptolepine 3, 4 5-methylquindolinone 4, 1 biscryptolepine 5, 5 cryptoquindoline 6, 1 cryptomisrine 7 6 etc., had been isolated from a medicinal plant Cryptolepis Sanguinolenta in Africa. (Figure 2) Many indolo [3,2-b]quinoline and indolo [3,2-b]quinolinone derivatives, especially the 11-substituted indolo [3,2-b]quinoline, showed remarkable pharmaceutical activity. For example, 11-[2-methoxy-4-(methylsulfonyl)phenyl]amino indoloquinoline 8 has shown to exhibit antitumor activity, 7,8 while both 11-(4-diethylamino)-2-methylbutylamino indoloquinoline 9 9 and 11-(4-hydroxylphenyl)amino indoloquinoline 10 10 have comparable activity with chloroquine to inhibit a multi-resistant Plasmodium falciparum strain (Figure 3). Most of the known 11-substituted indoloquinoline derivates were prepared from nucleophilic substitution of 11-chloroindoloquinoline, 7,10,11 and the later compounds could be readily obtained by treatment of indoloquinolinones with POCl 3. 7,10,12 Therefore the substituted indolo[3,2-b]quinolinones became With the purpose to synthesize the analogues of alkaloid biscryptolepine 5, cryptoquindoline 6 and cryptomisrine 7, we first need to prepare some substituted indolo [3,2-b]quinolinones as starting materials. Although some synthetic methods for the preparation of indolo [3,2-b]quinolinones have been developed, most of them started from the condensation of two o-aminoaryl carbonyl compounds. 7,12,13 Frequently encountered problems in these methods are the lack of commercially available starting materials. Several years ago, 14 we reported that the interaction of the Vilsmeier's reagents 12 and an organic base lead to the formation of 11-N-arylamino indolo[3,2-b]quinolinium salts 13 and /or indolo[3,2-b]quinolinium salts 14, and the compounds 13 or 14 could be readily demethylated by sodium iodide/ triphenylphosphine to give quindolines 15 or 16 respectively in high yields. (Scheme 1) Considering their electrophilic nature, the hydrolysis of quindolinium ions 13 and 14 would give rise to substituted quindolinones. Here we report our study on the hydrolysis or hydrolytic oxidation of indolo[3,2-b]quinolinium salts. Scheme 1 Results and DiscussionIn our earlier work, 14 we had noticed that the hydrolysis of indolo[3,2-b]quinolinium salt 13a (X = Me) in 10% NaOH aqueous solutio...