A culture broth of Streptomyces pilosus ETH 21748 is treated with Hyflo-Supercel and aqueous ferric sulfate, and the clear solution obtained is extracted with phenol-CHCl3 to obtain, after purification a crude mixture of ferrioxamins A, B, C, D1, D2, E and F. This crude product is chromatographed through Dowex 50 WX2 using an ammonium acetate buffer and the different ferrioxamins are separated. The treatment of ferrioxamin B (I) with aqueous NaOH gives a precipitate of Fe(OH)3 which is filtered off, and the remaining solution is then treated with HCl and extracted with phenol-CHCl3. Finally, this extract is worked up to give the pure product.

The reaction of 1-amino-5-nitropentane (I) with benzyloxycarbonyl chloride (A) by means of NaOH in water gives 1-carbobenzoxyamino-5-nitropentane (II), which by reduction with Zn and ammonium chloride in ethanol - water yields 1-carbobenzoxyamino-5-hydroxylaminopentane (III). The reaction of (III) with succinic anhydride (B) by means of NaOH in pyridine water affords 1-carbobenzoxyamino-5-(N-succinylhydroxylamino)pentane (IV), which is cyclized with hot acetic anhydride giving 2-(5-carbobenzoxyaminopentyl)-3,6-dioxotetrahydro-1,2-oxazine (V). The reaction of (V) with the nitroamine (I) by means of sodium methoxide in methanol yields 1-carbobenzoxy-6-hydroxy-16-nitro-7,10-dioxo-6,11-diazahexadecane (VI), which is reduced with Zn and acetylated as before affording 1-carboxybenzoxyamino-6-hydroxy-16-(N-acetylhydroxylamino)-7,10-dioxo-6,11-diazahexadecane (VII).

The acetylation of (III) as before gives 1-carbobenzoxyamino-5-(N-acetylhydroxylamino)pentane (X), which is debenzylated as usual yielding 1-amino-5-(N-acetylhydroxylamino)pentane (XI). Finally, this compound is condensed with (V) to afford (VII).

The debenzylation of (VII) by hydrogenation with H2 over Pd/C gives 1-amino-6-hydroxy-16-(N-acetylhydroxylamino)-7,10-dioxo-6,11-diazahexadecane (VIII), which condensed with (V) as before yields 1-carbobenzoxyamino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetrazaheptaeicosane (IX). Finally, this compound is debenzylated by means H2 over Pd/C.

A culture broth of Streptomyces pilosus ETH 21748 is treated with Hyflo-Supercel and aqueous ferric sulfate, and the clear solution obtained is extracted with phenol-CHCl3 to obtain, after purification a crude mixture of ferrioxamins A, B, C, D1, D2, E and F. This crude product is chromatographed through Dowex 50 WX2 using an ammonium acetate buffer and the different ferrioxamins are separated. The treatment of ferrioxamin B (I) with aqueous NaOH gives a precipitate of Fe(OH)3 which is filtered off, and the remaining solution is then treated with HCl and extracted with phenol-CHCl3. Finally, this extract is worked up to give the pure product.

A culture broth of Streptomyces pilosus ETH 21748 is treated with Hyflo-Supercel and aqueous ferric sulfate, and the clear solution obtained is extracted with phenol-CHCl3 to obtain, after purification a crude mixture of ferrioxamins A, B, C, D1, D2, E and F. This crude product is chromatographed through Dowex 50 WX2 using an ammonium acetate buffer and the different ferrioxamins are separated. The treatment of ferrioxamin B (I) with aqueous NaOH gives a precipitate of Fe(OH)3 which is filtered off, and the remaining solution is then treated with HCl and extracted with phenol-CHCl3. Finally, this extract is worked up to give the pure product.

The reaction of 1-amino-5-nitropentane (I) with benzyloxycarbonyl chloride (A) by means of NaOH in water gives 1-carbobenzoxyamino-5-nitropentane (II), which by reduction with Zn and ammonium chloride in ethanol - water yields 1-carbobenzoxyamino-5-hydroxylaminopentane (III). The reaction of (III) with succinic anhydride (B) by means of NaOH in pyridine water affords 1-carbobenzoxyamino-5-(N-succinylhydroxylamino)pentane (IV), which is cyclized with hot acetic anhydride giving 2-(5-carbobenzoxyaminopentyl)-3,6-dioxotetrahydro-1,2-oxazine (V). The reaction of (V) with the nitroamine (I) by means of sodium methoxide in methanol yields 1-carbobenzoxy-6-hydroxy-16-nitro-7,10-dioxo-6,11-diazahexadecane (VI), which is reduced with Zn and acetylated as before affording 1-carboxybenzoxyamino-6-hydroxy-16-(N-acetylhydroxylamino)-7,10-dioxo-6,11-diazahexadecane (VII).

The acetylation of (III) as before gives 1-carbobenzoxyamino-5-(N-acetylhydroxylamino)pentane (X), which is debenzylated as usual yielding 1-amino-5-(N-acetylhydroxylamino)pentane (XI). Finally, this compound is condensed with (V) to afford (VII).

The debenzylation of (VII) by hydrogenation with H2 over Pd/C gives 1-amino-6-hydroxy-16-(N-acetylhydroxylamino)-7,10-dioxo-6,11-diazahexadecane (VIII), which condensed with (V) as before yields 1-carbobenzoxyamino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetrazaheptaeicosane (IX). Finally, this compound is debenzylated by means H2 over Pd/C.

A culture broth of Streptomyces pilosus ETH 21748 is treated with Hyflo-Supercel and aqueous ferric sulfate, and the clear solution obtained is extracted with phenol-CHCl3 to obtain, after purification a crude mixture of ferrioxamins A, B, C, D1, D2, E and F. This crude product is chromatographed through Dowex 50 WX2 using an ammonium acetate buffer and the different ferrioxamins are separated. The treatment of ferrioxamin B (I) with aqueous NaOH gives a precipitate of Fe(OH)3 which is filtered off, and the remaining solution is then treated with HCl and extracted with phenol-CHCl3. Finally, this extract is worked up to give the pure product.

The reaction of 1-amino-5-nitropentane (I) with benzyloxycarbonyl chloride (A) by means of NaOH in water gives 1-carbobenzoxyamino-5-nitropentane (II), which by reduction with Zn and ammonium chloride in ethanol - water yields 1-carbobenzoxyamino-5-hydroxylaminopentane (III). The reaction of (III) with succinic anhydride (B) by means of NaOH in pyridine water affords 1-carbobenzoxyamino-5-(N-succinylhydroxylamino)pentane (IV), which is cyclized with hot acetic anhydride giving 2-(5-carbobenzoxyaminopentyl)-3,6-dioxotetrahydro-1,2-oxazine (V). The reaction of (V) with the nitroamine (I) by means of sodium methoxide in methanol yields 1-carbobenzoxy-6-hydroxy-16-nitro-7,10-dioxo-6,11-diazahexadecane (VI), which is reduced with Zn and acetylated as before affording 1-carboxybenzoxyamino-6-hydroxy-16-(N-acetylhydroxylamino)-7,10-dioxo-6,11-diazahexadecane (VII).

The acetylation of (III) as before gives 1-carbobenzoxyamino-5-(N-acetylhydroxylamino)pentane (X), which is debenzylated as usual yielding 1-amino-5-(N-acetylhydroxylamino)pentane (XI). Finally, this compound is condensed with (V) to afford (VII).

The debenzylation of (VII) by hydrogenation with H2 over Pd/C gives 1-amino-6-hydroxy-16-(N-acetylhydroxylamino)-7,10-dioxo-6,11-diazahexadecane (VIII), which condensed with (V) as before yields 1-carbobenzoxyamino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetrazaheptaeicosane (IX). Finally, this compound is debenzylated by means H2 over Pd/C.