Biotransformation and stereoselective synthesis of pharmaceutical molecules from linoleic acid

• Main Authors: Omar, Muhammad Nor, Muhd Nor, Nor Nazuha, Moynihan, Humphrey, Hamilton, Richard J.
• Format: Article
• Language: English
• Published: Asian Network for Scientific Information 2007
• Subjects: QD Chemistry
• Online Access: http://irep.iium.edu.my/24445/1/Biotransformation_and_stereoselective_synthesis_of_pharmaceutical_molecules_from_linoleic_acid.pdf; http://irep.iium.edu.my/24445/; http://docsdrive.com/pdfs/ansinet/biotech/2007/283-287.pdf

The biotransformation of linoleic acid 1 using immobilised soybean lipoxygenase in a dimethyl sulfoxide (DMSO) containing medium followed by sodium borohydride reduction afforded 13(S)-hydroxy-octadeca-9(Z),11(E)-dienoic acid 13(S)-HODE 2 in 69% yield. After methylation, methyl 13(S)-HODE was subjected to epoxidation using tert-butyl hydroperoxide (TBHP) in the presence of vanadyl acetylacetonate or titanium (IV) isopropoxide with D-(-)- or L-(+)-diisopropyl tartrate. Epoxidation catalysed by titanium (IV) isopropoxide/D-(-)-isopropyl tartarate gave predominantly epoxide 3 (in 75% yield) while treatment of 2 with TBHP in the presence of titanium (IV) isopropoxide and L-(+)-diisopropyl tartrate gave preferentially epoxide 4 in 73% yield. Meanwhile, epoxidation of 2 with TBHP in the presence of vanadyl acetylacetonate gave predominantly epoxide 3 in 72% yield. The fluoro-derivatives 8, 9 and 10 were obtained in high yield when hydroxy-derivative 2, 3 and 4 were converted into their trimethylsilyl derivatives 5, 6 and 7 before treating with diethylaminosulphur trifluoride. Treatment of epoxide 4 with acetamide in dimethyl formamide (DMF) afforded a heterocyclic 2-oxazoline 11 in 73% yield.