AngewanON, dte ^L Communications Natural Products D01: 10.1002/anie.201305697 Occurrence of the Synthetic Analgesic Tramadol in an African Medicinal Plant** Ahcène Boumendjel, Germain Sotoing Taïwe, * Elisabeth Ngo Bum, Tanguy Chabrol, Chantal Beney, Valérie Sinniger, Romain Haudecoeur, Laurence Marcourt, Soura Challal, Emerson Ferreira Queiroz, Florence Souard, Marc Le Borgne, Thierry Lomberget, Antoine Depaulis, Catherine Lavaud, Richard Robins, Jean-Luc Wolfender, Bruno Bonaz and Michel De Waard* initiating a research program aimed at discovering natural products as pain relievers, we focused our attention on the sub-Saharan Nauclea latifolia Sm. (Rubiaceae) plant, commonly known as African peach or pincushion tree. This plant has a long tradition of use by local populations for the treatment of a wide diversity of illnesses, including severe digestive problems, neurological disorders and infectious diseases1" In Cameroon, the plant is used to treat pain, malaria, fever, epilepsy, and infantile convulsions. We were particularly interested in the traditional use of the root bark of N. latifolia in pain relief. Previous phytochemical investigation of N. latifolia led to the identification of alkaloids, mostly naucleamides, as the main cor • *-f1411 frnm this niant have.. shown antinvrmtica( moderate to severe pain without any known side effectselit was designed by a simplification of the structure of morphine that kept the pharmacophoric elements responsible for the analgesic effect. Herein, we describe the isolation of tramadol from the root bark of N. latifolia, and the different methods used to prove the authenticity of its natural origin. The methanolic extract of the root bark of N. latifolia showed potent analgesic activity in an antinociceptive in vivo assay. To identify the active compounds, the extract was investigated through a bio-guided isolation procedure. The methanolic extract was submitted to HPLC fractionation using a reverse-phase column (Supporting Information, Figure 1 a). The submitted to the anti-nociceptive I that the hinactivitv rpsicInci within Click for Article Access Options