Menthol Warfarin

The transformation could also be performed using a chiral enantiopure enol ether as dienophile. The best results were achieved with the isopropenyl ether 182b derived from cheap and commercially available (—)-(lR,2S,5R)-menthol. The cycloadduct was obtained with an endo/exo-selectivity of 4.1 1 and an induced dia-stereoselectivity of 88 12. Treatment of 178b with trifluoroacetic acid/water 19 1 provided (S)-warfarin 175 in an overall yield of 61% referred to 4-hydroxy coumarin 55 and an enantiomeric excess of 76% (HPLC), which could be increased to 95% ee by recrystallization using the purified endo-product 178b as substrate for the hydrolysis. In the same manner (S)-coumachlor 176 and (S)-acenocoumarol 177 were obtained with 56% overall yield and 93% ee and 59% overall yield and 95% ee, respectively. 

A man had a reduction in the effects of warfarin, which were attributed to the usie of menthol cough lozenges during a flu-like ill-... 

A 57-year-old man taking warfarin 49 mg weekly with an INR in the range of 2.28 to 2.68 for the previous 3 weeks was found to have an INR of 1.45. He had been unwell with a flu-like illness over the past week, for which he had been taking about 6 Halls menthol cough lozenges (eough... 

Kassebaum PJ, ShawDL, TomichDJ. Possible warfarin interaction witii menthol cough drops. Am Pharmacother (2005) 39, 365-7. 

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