Formation of Trideuteromethylated Artifacts of Pyrrole-Containing Natural Products

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2024-02, Vol.87 (2), p.415-423
• Main Authors: Orfanoudaki, Maria, Akee, Rhone K., Martínez-Fructuoso, Lucero, Wang, Dongdong, Kelley, James A., Smith, Emily A., Henrich, Curtis J., Schnermann, Martin J., O’Keefe, Barry R., Grkovic, Tanja
• Format: Article
• Language: English
• Subjects: Biological Products - pharmacology; Dimethyl Sulfoxide - chemistry; Humans; iron; metabolites; methanol; neoplasm cells; Pyrroles - chemistry; solvents; Solvents - chemistry
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/acs.jnatprod.3c01113

Pyrrole-containing natural products form a large group of structurally diverse compounds that occur in both terrestrial and marine organisms. In the present study the formation of trideuteromethylated artifacts of pyrrole-containing natural products was investigated, focusing on the discorhabdins. Three deuterated discorhabdins, 1, 3, and 5, were identified to be isolation procedure artifacts caused by the presence of DMSO-d 6 during NMR sample preparation and handling. Three additional semisynthetic derivatives, 7–9, were made during the investigation of the mechanism of formation, which was shown to be driven by trideuteromethyl radicals in the presence of water, methanol, TFA, and traces of iron in the deuterated solvent. Generation of trideuteromethylated artifacts was also confirmed for other classes of pyrrole-containing metabolites, namely, makaluvamines, tambjamines, and dibromotryptamines, which had also been dissolved in DMSO-d 6 during the structure elucidation process. Semisynthetic discorhabdins were assessed for antiproliferative activity against a panel of human tumor cell lines, and 14-trideuteromethyldiscorhabdin L (3) averaged low micromolar potency.