- Multistage process for the preparation of highly pure deferoxamine mesylate salt
-
The present invention provides a purification process whereby deferoxamine B produced by a microorganism and in mixture with other polyhydroxamates produced by the microorganism may be converted into its mesylate salt substantially free of the other polyhydroxamates and substantially free of chloride ion. The process includes adsorption and desorption of the deferoxamine B on an adsorption resin, direct precipitation of the deferoxamine free base out of the eluent from the adsorption resin, contacting of the deferoxamine B free base with methanesulfonic acid and isolation of the deferoxamine B mesylate salt by precipitation. This process minimizes decomposition of deferoxamine B.
- -
-
-
- A versatile synthesis of deferrioxamine B
-
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.
- Bergeron,McManis,Phanstiel IV,Vinson
-
p. 109 - 114
(2007/10/02)
-
- Method for the synthesis of desferrioxamine B and analogs thereof
-
Disclosed is a synthesis of desferrioxamine B and analogs and homologs thereof beginning with the generation of the O-protected N-(4-cyanobutyl)hydroxylamine which is acylated at the O-benzylhydroxylamine nitrogen with either succinic or acetic anhydride. The resulting half-acid amide or amide respectively, is subjected to a series of high yield condensations and reductions which provide desferrioxamine B in 45% overall yield. Finally, a desamino analog of desferrioxamine is prepared in order to demonstrate the synthetic utility of the scheme as applied to desferrioxamine derivatives.
- -
-
-
- An Efficient Total Synthesis of Desferrioxamine B
-
The total syntheses of the microbial iron chelator desferrioxamine B hydrochloride and some analogues are described.The syntheric scheme is highly flexible, providing access to dihydroxamate, trihydroxamate, tetrahydroxamate, and higher homologues of desferrioxamines.The procedure also allows for access to primary amino nitrogen functionalized desferrioxamine.The scheme is predicated on the generation of the key intermediate O-benzyl-N-(4-cyanobutyl)hydroxylamine, which is acylated at the O-benzylhydroxylamine nitrogen with either succinic or acetic anhydride.The resu lting half acid amide or amide, respectively, is subjected to a series of high-yield condensations and reductions that provide desferrioxamine in 45percent overall yield.Finally a desamino analogue of desferrioxamine is prepared in order to demonstrate the synthetic utility of the scheme as applied to desferrioxamine derivatives.
- Bergeron, Raymond J.,Pegram, Joseph J.
-
p. 3131 - 3134
(2007/10/02)
-