Isolation and structural characterization of two tadalafil analogs found in dietary supplements

During routine screenings of two "libido enhancer" dietary supplements using LC-MS(n), two compounds were detected that displayed structural similarities to tadalafil. These compounds were isolated from the supplements using high-performance liquid chromatography with fraction collection, and were characterized further using accurate mass determination and NMR. "Compound 1" had an m/z of 434 for the [M+H]⁺ ion, with a corresponding chemical formula of C₂₄H₂₄N₃O₅. "Compound 2" had an m/z of 432 for the [M+H]⁺ ion, with a corresponding chemical formula of C₂₅H₂₆N₃O₄. Although mass spectrometry indicated that these modifications occurred in place of the -CH₃ found on the pyrazinopyridoindole-1,4-dione of tadalafil, NMR was required to elucidate the correct configurations of these substitutions. The data obtained using NMR indicated that the structure of the -C₃H₇O moiety found in Compound 1 was 2-hydroxypropyl, and the -C₄H₉ in Compound 2 was n-butyl. These new analogs were given the names 2-hydroxypropylnortadalafil and n-butylnortadalafil, respectively.