Synthesis of lesquerella α-hydroxy phosphonates

Abstract

Hydroxy fatty acids (HFAs) have found a number of uses in today's market, with uses ranging from industrial materials to pharmaceuticals. Castor oil, which is obtained from castor seeds, has served as a source of a versatile HFA; its principle component, ricinoleic acid, can be isolated from castor oil and has been modified extensively for a number of applications. 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 allergens. Lesquerella oil, obtained from seeds of the Lesquerella fendleri species, has been identified as the most promising alternative source of HFAs. Lesquerolic acid, the primary HFA found in lesquerella oil, is also most homologous to ricinoleic acid; the only structural difference between the two is that lesquerolic acid possesses two additional methylene groups on the carboxyl end of the molecule. This structural and chemical similarity further suggests lesquerella oil and its derivatives may function as a competitive alternative to castor oil. Unfortunately, the desired HFA, lesquerolic acid, constitutes approximately 50% of lesquerella oil where castor oil contains approximately 90% of the desired HFA. This difference in desired HFA abundance in lesquerella oil required more extensive purification measures and careful identification of the correct component. Additionally, α-hydroxy phosphonates and their corresponding phosphonic acids are functional moieties that have been shown to display a wide variety of biological activities, as enzyme inhibitors, pesticides, antibiotics and anti-cancer therapeutics. We previously reported the synthesis of two families of α-hydroxy phosphonic acids based on ricinoleic acid: a family that retains the cis alkene found in ricinoleic acid and one where the alkene has undergone hydrogenation to produce a saturated α-hydroxy phosphonic acid. We now report the purification of the desired lesquerolic acid component of lesquerella oil and synthesis of lesquerolic acid-derived α-hydroxy phosphonates, both the unsaturated and saturated families. As with the ricinoleic acid-based compounds, the lesquerolic acid-based compounds have been produced in high yields and high purity, and the synthesis of these compounds is reported in this manuscript.