Ifetroban sodium

Mueller, R.H., A Practical Synthesis of Ifetroban Sodium. In Process Chemistry in the Pharmaceutical Industry (K.G. Gadamasetti, ed.). Chap. 3, Marcel Dekker, Inc., New York, 1999, pp. 37-55. 

A tetrahydropyran that inhibits leukotriene biosynthesis Asymmetric synthesis of2-methyl-tetrahydropyran-4-one by kinetic resolution Part VI - Asymmetric Desymmetrisation of a Diels-Alder Adduct Ifetroban sodium a thromboxane receptor antagonist A laboratory synthesis starting with a Diels-Alder reaction Desymmetrisation of a symmetrical anhydride with a chiral Grignard reagent Laboratory and process routes compared Part VII - Asymmetric Synthesis of A Bicyclic 3-Lactone Lactacystin a naturalproteasome inhibitor... 

The problem with this synthesis is its great length (23 steps altogether) caused by the repeated changes of oxidation level of the functional groups. The overall yield is less than 3% but even so it was used to make some 20 kg of ifetroban sodium. As the compound became a more likely drug candidate, a more efficient synthesis was clearly needed. 

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