Syntheses and Sleeping-Time-Prolonging Effect of Nitramarine and Related Compounds

Nitramarine (1), which possesses a β-carboline nucleus, was synthesized by two routes. First, we applied an intramolecular thermal cyclization of the 1-azahexatrienesystem in heteroaromatics such as 2. Although no intermediate (9 or 10) could be isolated, heating of 7 in toluene or of 8 in odichlorobenzene in the presence of hydroxylamine gave nitramarine (1) or its derivative (11), respectively. On the other hand, the Pictet?Spengler reaction between (±) -tryptophan ethyl ester (12) and 2-quinoline carbaldehyde (13) gave nitramarine carboxylic acid ethyl ester (11). Subsequent hydrolysis followed by decarboxylation gave 1. Nitramarine carboxylic acid (15) and carboxamide (16) were found to prolong the sleeping time of mice.