Reactions and Synthetic Applications of β-Keto Sulfoxides. X. Synthesis of Ellipticine Analogs modified at the 5-Position

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A β-keto sulfoxide (12) derived from ethyl indolebutyrate (11) and methyl methylthiomethyl sulfoxide (MMTS) was cyclized to 4-methyl-1, 1-bismethylthio-2-oxo-1, 2, 3, 4-tetrahydrocarbazole (13) by treatment with p-toluenesulfonic acid (TsOH). Introduction of an acetic ester unit at the carbonyl group with tert-butyllithioacetate gave a key intermediate (14) to all the 5-modified ellipticine analogs. An acid-catalyzed aromatization with acetic acid in xylene gave tert-butyl 4-methyl-1-methylthiocarbazole-2-acetate (15), which was readily converted to 5-methylthioellipticine (7) through a series of usual reactions. The overall yield of 7 from 11 was 25-27%. Desulfurization of 7 with Raney nickel in xylene gave 5-norellipticine (8). The bismethylthio group in 14 was easily hydrolyzed with TsOH in methanol to give a 1-keto compound (21), which was aromatized to a lactone (22), and then converted to 5-methoxyellipticine (9). Hydrolysis of 9 with 47% hydrobromic acid gave 5-hydroxyellipticine (10).