New preparative routes to isosorbide 5-mononitrate

Abstract

Three new methods for the preparation of the vasodilator isosorbide 5-mononitrate are described. In the first method enzymatic regioselective acetylation of isosorbide gave isosorbide 2-butyrate. Nitration and deprotection of this material afforded isomerically pure isosorbide 5-mononitrate in high overall yield. Secondly, regioselective hydrogenation of isosorbide dinitrate over platinum oxide (PtO2) furnished the 5-mononitrate in 45% yield. Similarly, regioselective reduction of the dinitrate was achieved using sodium borohydride (NaBH4) activated with cobalt or iron phthalocyanine. All three methods show advantages over existing procedures.