The Alkaloids of Tribulus terrestris: A Revised Structure for the Alkaloid Tribulusterine

The fruit of the plant Tribulus terrestris is well known as a traditional Chinese medicine with a myriad of reported uses. Herbal medicine preparations are becoming available for many uses including body building and for stimulating spermatogenesis and libido. In addition, the whole live plant causes significant sheep losses in certain regions of Australia when conditions for growth are favoured. Chronic poisoning of the sheep occurs, characterised by a distressing irreversible asymmetric locomotor disorder. The symptoms, which have some similarities to those of Parkinson’s disease in humans, are indicative of a localised interference with the central nervous system, possibly with serotonin-associated neurones. On the basis of other studies, it was thought that the neurotoxic agent may be the -carboline alkaloid, tribulusterine, which had been isolated in very low yield from the fruit of T. terrestris. This investigation developed an efficient synthesis of tribulusterine in order to confirm its structure and provide sufficient material for animal toxicity studies. A successful synthesis of the target alkaloid with structural confirmation by NMR and X-ray crystallography indicated that a structural revision for the reported natural alkaloid was necessary. The same synthetic strategy when applied to the synthesis of perlolyrine confirmed that this closely related -carboline was the natural Tribulus constituent.