A versatile synthesis of deferrioxamine B

Article abstract of DOI:10.1021/jo00106a022

A new and versatile route to N'-[5-[[4-[[5-(acetylhydroxyamino)pentyl]amino]-1,4-dioxobutyl]-hydrox yamino]pentyl]-N-(5-aminopentyl)-N-hydroxybutanediamide, deferrioxamine B (DFO), is described. The key improvement over the two prior routes was replacement of the nitrile in 2 with a tert-butoxycarbonyl-protected amino terminus. Elimination of the nitrile improved the kinetics of hydrogenation in that the benzyl groups of 12 were cleaved more rapidly than saturation of the cyano group of 2, and a potential overreduction byproduct (4) was thus avoided. N-(Benzyloxy)-1,5-diaminopentane (6) was selectively protected at the primary amino site with a tert-butoxycarbonyl (BOC) group, providing 7. This was reacted at the (benzyloxy)amine with succinic anhydride to produce carboxylic acid 8, which was in turn acylated regiospecifically with diamine 6 at the primary amine to give (benzyloxy)amine 9. The previous two steps were reiterated to afford DFO reagent 11. This synthon allows for modification of DFO at either end of the molecule, thus providing more flexibility in accessing DFO analogues than any prior route. Acetylation of 11, followed by hydrogenolysis and tert-butoxycarbonyl group removal, furnished DFO.