Synthesis of Lesquerella-based bisphosphonates

Authors: BOON, LAURALEE - Knox College; BAMERT, SIERRA - Knox College; FAYER, EFFRAT - Knox College; COLEY, CHELSEA - Knox College; HENRY, SHANNON - Knox College; CERMAK, DIANA - Knox College; Cermak, Steven - Steve

Submitted to: Journal of the American Oil Chemists' Society
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2023
Publication Date: 11/24/2023
Citation: Boon, L.M., Bamert, S.R., Fayer, E.L., Coley, C.L., Henry, S.M., Cermak, D.M., Cermak, S.C. 2023. Synthesis of Lesquerella-based bisphosphonates. Journal of the American Oil Chemists' Society. 101(3):335-344. https://doi.org/10.1002/aocs.12760.
DOI: https://doi.org/10.1002/aocs.12760

Interpretive Summary: Castor oil, which is obtained from castor seeds usually imported from India, serves as the main U.S. source of hydroxy fatty acids (HFA) or ricinoleic acid. HFA has been isolated and modified extensively for several applications ranging from industrial materials to pharmaceuticals. Unfortunately, castor seeds also contain several undesirable compounds which pose severe health risks, including ricin, an unusually stable, deadly protein; ricinine, a poisonous alkaloid; and several other allergens. The structural and chemical similarity of the primary HFA found in lesquerella, a U.S. crop, suggests that lesquerella oil and its derivatives may function as a competitive alternative to castor oil. Unfortunately, there is a significant difference in desired HFA abundance in lesquerella oil (50%) than castor oil (90%), requiring more extensive purification measures and careful identification of the correct components of lesquerella. In this research, we report the purification and synthesis, in high yields and high purity, of the desired HFA in lesquerella. This work is significant because it opens the potential for HFA from lesquerella to function effectively and replace the use of castor oil in a wide variety of biological activities, such as enzyme inhibitors, pesticides, antibiotics, and anti-cancer therapeutics.

Technical Abstract: Hydroxy fatty acids (HFAs) have found wide use in today’s market, ranging from industrial materials to pharmaceuticals. Castor oil, which is obtained from castor seeds, has served as a primary source of the most common HFA, ricinoleic acid, but also contains several undesirable compounds which pose severe health risks, the most notable being ricin, an unusually stable, toxic protein. A promising HFA alternative is lesquerella oil, an oil obtained from seeds of the Lesquerella fendleri species. Lesquerella oil is mainly comprised of lesquerolic acid, an HFA that is structurally similar to ricinoleic acid, the only difference being that lesquerolic acid possesses two additional methylene groups on the carboxyl end of the molecule. In addition, the bisphosphonate moiety has been shown to display interesting biological activities, primarily as osteoporosis drugs and anti-cancer therapeutics. The synthesis of lesquerella-based bisphosphonates, both an unsaturated and saturated series, have been produced in high yields and high purity and are reported here.