1.2.3.4- Tetrahydro-l -keto-p-carboline

The action of a solution of potash in amyl alcohol on rutaecarpine produces anthranilic acid and a second acid which, when boiled with hydrochloric acid, is readily decarboxylated to tryptamine (6, 25, 94, 134, 135, 169). A close relationship between rutaecarpine and evodiamine was demonstrated by fusion of isoevodiamine hydrochloride. Rutaecarpine was formed with liberation of chloromethane. A number of syntheses of (63) have been reported 101, 135, 161), including some under so-called physiological conditions. Some of the more recent examples will be mentioned. Kametani et al. 102,108) obtained (63) in 80% yield through a regiospecificH s+n s cycloaddition of a keteneimine (generated in situ by extrusion of sulfur dioxide from the sulfmamide anhydride of anthranilic acid) with 3,4-dihydro-p-carboline or with 1,2,3,4-tetrahydro-l-keto-P-carboline 109) (also called 1,2,3,4-tetrahydronorharman-l-one or, as in Chemical Abstracts, 2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-one) ac-... 

X OMe), a singlet at 8 5.23 (NMe), and a complex multiplet between 5 7.2 and 8.2 corresponding to six aromatic protons. Treatment with potassium hydroxide in refluxing amyl alcohol afforded 1,2,3,4-tetrahydro-l-keto-P-carboline and 6-methylaminoveratric acid. The structure of euxylophorine A was confirmed by condensation of l,2,3,4-tetrahydro-l-keto- 3-carboline with methyl 6-methylaminoveratrate (52). 

Euxylophoricine F (90) exhibits the same uv spectrum as the other euxylophoricines. Methylation with methyl iodide and potassium carbonate yields Ni3-methyleuxylophoricine A, indicating that euxylophoricine F is a 2,3-disubstituted rutaecarpine derivative. The structure was confirmed by synthesis. Condensation of 4-benzyloxy-5-methoxy-anthranilic acid methyl ester with 1,2,3,4-tetrahydro-l-keto-p-carboline in the presence of phosphorus oxychloride and subsequent hydrogenolysis gave (90). 

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