Green Chemical Synthesis Method of Ibuprofen Piconol
Haricharan Raju, C. M., et al. Synthetic communications, 2005, 35(2), 209-212.
Ibuprofen Piconol is the piconol derivative of ibuprofen and has been used as a topical anti-inflammatory agent in the treatment of acne. The traditional synthesis of ibuprofen piconol involves the use of thionyl chloride to prepare acid chloride 4, followed by treatment with pyridine 2-methanol, with an atom economy of 68% (Scheme 1). This work reports a simple one-step method for the synthesis of ibuprofen piconol using environmentally friendly catalysts such as montmorillonite K-10 and resins with an atom economy of up to 94%.
Synthetic procedure of ibuprofen piconol
· A mixture of Ibuprofen (4.1 g, 20 mmol), piconol (2.4 g, 22 mmol) and Montmorillonite clay K-10 (20% w/w with respect to ibuprofen) in toluene was refluxed for 18 hours. The reaction progress was monitored using thin-layer chromatography.
· After filtration, the filtrate was washed with sodium bicarbonate and oxalic acid solutions. The organic layer was then concentrated under reduced pressure to obtain the crude product, which was further purified by distillation (5.7 g, 97% yield).
· In addition, the addition of catalytic amounts of p-toluenesulfonic acid in xylene as a solvent improved the recovery of the product.
Ibuprofen Piconol Discovered as Chemical Inhibitor in Mechanistic Study of GDAP1 in csg2Δ Cells
Binięda, Katarzyna, et al. International Journal of Molecular Sciences, 2021, 22(2), 914.
To further dissect GDAP1-dependent calcium hypersensitivity suppression in csg2Δ mutants, a chemical suppressor screen was used. The study found that ibuprofen piconol is an inhibitor of the csg2Δ growth defect on Ca2+ ion-containing media.
Drug screening of library compounds
· The Prestwick Drug Repurposing Library (Prestwick Chemical Library), previously used for this type of screening, containing drugs approved for human use, was screened.
· Library compounds were used on filter discs placed on top of solid media to identify active compounds. Growth zones around the filter indicated the presence of active compounds after 3-5 days.
· Two drugs, cyclosporine A and ibuprofen piconol, were found to suppress the csg2Δ growth defect on Ca2+ ion containing media. Among them, ibuprofen piconol is a nonsteroidal anti-inflammatory agent that also acts as a phospholipase inhibitor.
· In conclusion, GDAP1 expression suppresses csg2Δ not by sphingolipid biosynthesis, but likely through a conserved pathway connected to calcium homeostasis, phospholipase inhibition, or both.