Conolidine is found in a wide number of species in the genus Tabernaemontana, although most studies only report its presence in Tabernaemontana divaricata. The peak concentration of conolidine is extremely low1, and its presence is probably below the level of detection of many analytical laboratories focusing on primary metabolites.
“The natural product conolidine was originally isolated in extremely small quantities—just 0.00014% yield—from the stem bark of the flowering tropical plant Tabernaemontana divaricata. The low natural abundance of the compound has hindered the study of its potential therapeutic properties.”
Studies note conolidine in Tabernaemontana bufalina2, Tabernaemontana Sanaho3, and staff at Phylochem have detected it in a number of other species in the genus, confirming that the presence of conolidine is not unique to a single species. As well as Tabernaemontana, it is within the realm of possibility that it may be found in other genera such as Aspidosperma.
Phylochem leverages its pilot-scale extraction facility for sample preparation, allowing sample sizes of 100kg of plant material to be screened, adding three or four orders of magnitude over typical sample batch sizes. Working with very low yields is challenging and means operating around the level of detection. By utilizing larger-scale extraction equipment, the laboratory workload is simplified.
Because plant yields are so low, chemical synthesis appears to be the most economic means of production, and numerous synthesis methods are published. To provide a viable natural source of conolidine outside of biotechnology, Phylochem needs to increase the yields by at least 100-fold to viably produce conolidine from natural sources.
An alternative to synthesis is semi-synthesis using stemmadenine as a starting material. Phylochem produces stemmadenine from Tabernamontana sources and is able to supply stemmadenine.
Phylochem is researching conolidine production with a view to scaling up production in the mid-term.
1 Reisman, S. E. (2011). New lead for pain treatment: The synthesis of conolidine, a scarce, naturally occurring compound. Nature, 473, 458-459. Read the full paper.
2 Shi, B.-B., Chen, J., Bao, M.-F., Zeng, Y., & Cai, X.-H. (2019). Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activity. Phytochemistry, 162, 45-51. Read the full article.
3 Luzuriaga-Quichimbo, C.X., Ruiz-Téllez, T., Blanco-Salas, J., & Cerón Martínez, C.E. (2017). Ethnobotany and Conservation of Sikta (Tabernaemontana Sanaho Ruiz & Pav.) in Canelo-Kichwa Communities from Amazonian Ecuador. Presented at the 4-7 July 2017 conference in Madrid, Spain. Read the full paper.