TOTAL SYNTHESIS OF THE 5-HT3 RECEPTOR ANTAGONIST PALONOSETRON

A short and efficient synthetic route to the 5-HT3 receptor antagonist s 1 and 2 (palonosetron) was developed. The novel adjustment of the ox idation states at the necessary centers of imide 7 was accomplished by hydrogenation, selective sodium borohydride reduction, and dehydratio n to yield 1. The sodium borohydride reduction of imide 8 was selectiv e for the C-3 carbonyl versus the C-l carbonyl next to the aromatic ri ng to give the hydroxy compound 9. It was essential to keep the sodium borohydride reduction free of oxygen, or diols 10a and 10b were forme d as significant byproducts.