The Tramadol origin: the end of a story or an endless controversy?

In 2013, Tramadol, a fully synthetic drug was extracted from the roots of an African shrub named Nauclea latifolia [1]. As it could be expected, this major discovery has stimulated both considerable excitement and controversy about its natural origin. In 2014, the presence of tramadol in the roots of the plant was suggested to be an anthropogenic contamination due to ethno-veterinary practices [2]. Clearly, further investigations are required in order to decipher the Tramadol origin. Hence, we have investigated 13 Nauclea latifolia roots collected at different areas of the national Bénoué park in Cameroon (designated by the UNESCO as a Biosphere reserve). HRMS analyses showed the occurrence of tramadol in all methanolic extracts of Nauclea latifolia. The new tramadol-targeted isolation procedure was carried out by semi-preparative HPLC with dry-load injection of the sample and the structure was confirmed by 1 D and 2 D NMR spectroscopic methods. Highly pure tramadol was isolated and is being analyzed by the ¹⁴C accelerator mass spectrometry in order to determine the radiocarbon content in the tramadol isolated from Nauclea latifolia versus synthetic Tramadol. Indeed, natural products, recently biosynthesized should contain radiocarbon and synthetic compounds (petroleum derived molecules) should not contain ¹⁴C as the latter is decayed.

Fig. 1

• References

• 1 Boumendjel A, Sotoing Taïwe G, Ngo Bum E, Chabrol T, Beney C, Sinniger V. et al. Occurrence of the Synthetic Analgesic Tramadol in an African Medicinal Plant. Angew Chem Int Ed 2013; 52: 11780-11784
• 2 Kusari S, Tatsimo SJN, Zühlke S, Talontsi FM, Kouam SF, Spiteller M. Tramadol-A True Natural Product? Angew Chem Int Ed 2014; 53: 12073-12076