Selective Methylmagnesium Chloride Mediated Acetylations of Isosorbide: A Route to Powerful Nitric Oxide Donor Furoxans

Isosorbide was functionalized with furoxan for the first time to give adducts that release nitric oxide up to 7.5 times faster than the commercial vasodilator, isosorbide-5-mononitrate (Is5N). The synthesis was facilitated by MeMgCl-mediated selective acetylation of isosorbide or selective deacetylation of isosorbide-2,5-diacetate, which was rationalized in terms of a more stable 5-alkoxide magnesium salt using DFT. Isosorbide-furoxans are safer to handle than Is5N due to greater thermal stability.