Amines warfarin anticoagulants

A typical procedure for the synthesis of warfarin anticoagulant according to Feng et al. s report." A mixture of C2-symmetric secondary amine amide catalysts (6.0 mg, 0.02 mmol), succinic acid (1.2 mg, 0.01 mmol), 4-hydroxycoumarin (16.2 mg, 0.10 mmol), and benzylideneacetone (0.15 mmol) in -butyl alcohol (1.0 mL) with H2O (50 jlL) was added to a test tube. The resulting mixture was stirred at 40°C for 12 hours and purified directly by column chromatography on silica gel... 

Because rodent populations world-wide were becoming resistant to the widely used Warfarin-type anticoagulant poisons, a search was initiated to find a rodenticide with a different mode of action one that would be effective against these resistant rodents. This search led to the discovery of the toxic nature of a family of diphenyl amines which act as uncouplers of oxidative phosphorylation. A structure-activity relationship (SAR) study was undertaken to choose a derivative that would be both poisonous to rodents but still readily consumed by them. This approach led to the discovery of bromethalin,... 

Mei and coworkers utilised primary amine thiourea 44 based on the (IS,25 )-diphenylethylene-l,2-diamine backbone for the enantioselective Michael reaction between 4-hydro>ycoumarin and a,p-unsaturated ketones (Scheme 19.49). The products were isolated in high to excellent yields (up to 97%) and in good to high enantiomeric excesses (up to 95% enantiomeric excess). This method gives access to enantiopure (S)-warfarin, which is an anticoagulant agent. 

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