Desferrioxamine, Deferoxamine, ICL-749B(depot formulation), CGH-749B(depot formulation), DFO, Ba-33112(mesylate), Ba-29837(HCl), NSC-527604, Desferin, Desferal, -Drug Synthesis Database

【结构式】

【药物名称】Desferrioxamine, Deferoxamine, ICL-749B(depot formulation), CGH-749B(depot formulation), DFO, Ba-33112(mesylate), Ba-29837(HCl), NSC-527604, Desferin, Desferal

【化学名称】N-[5-[3-[(5-Aminopentyl)hydroxycarbamoyl]propionamido]pentyl]-3-[[5-(N-hydroxyacetamido)pentyl]carbamoyl]propionohydroxamic acid

【CA登记号】70-51-9, 1950-39-6 (HCl), 138-14-7 (mesylate)

【分子式】C₂₅H₄₈N₆O₈

【分子量】560.69671

【开发单位】Novartis (Originator)

【药理作用】Antagonists to Metals, Specific Antidotes, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Antimetabolites, APP Expression Inhibitors, Metal Chelators

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

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.

参考文献中间体

【1】 Bickel, H.; et al.; 260. Stoffwechselprodukte von actinomyceten. Uber die isolierung und charakterisierung der ferrioxamine A-F, neuer wuchsstadde der sideramin-gruppe. Helv Chim Acta 1960, 43, 2118-28.
【2】 Bickel, H.; et al.; 261. Stoffweschselprodukte von actinomyceten, Uber die konstitution von ferrioxamine B. Helv Chim Acta 1960, 43, 2129-38.
【3】 Bickel, H.; et al.; 153. Stoffweschselprodukte von mikroorganismen. Zur henntnis von desferrioxamin B. Helv Chim Acta 1963, 46, 1385-89.
【4】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Hopkins, S.J.; Liposome-Entrapped Desferrioxamine deferoxamine. Drugs Fut 1979, 4, 7, 500.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	33386	iron(3+) 30-amino-2,10,13,21,24-pentaoxo-3,9,14,20,25-pentaazatriacontane-3,14,25-triolate		C₂₅H₄₅FeN₆O₈	详情	详情

合成路线2

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).

参考文献中间体

【1】 Prelog, V.; Walser, A.; 75. Stoffweschselprodukte con actinomyceten. Uber die synthese der ferrioxamine B und D1. Helv Chim Acta 1962, 45, 631-637.
【2】 Bickel, H.; et al.; 153. Stoffweschselprodukte von mikroorganismen. Zur henntnis von desferrioxamin B. Helv Chim Acta 1963, 46, 1385-89.
【3】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Hopkins, S.J.; Liposome-Entrapped Desferrioxamine deferoxamine. Drugs Fut 1979, 4, 7, 500.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	11291	Dihydro-2,5-furandione; Succinic anhydride	108-30-5	C₄H₄O₃	详情	详情
(A)	24261	1-[2-(chlorooxy)-2-oxoethyl]benzene		C₈H₇ClO₂	详情	详情
(I)	33387	5-nitropentylamine; 5-nitro-1-pentanamine		C₅H₁₂N₂O₂	详情	详情
(II)	33388	benzyl 5-nitropentylcarbamate		C₁₃H₁₈N₂O₄	详情	详情
(III)	33389	benzyl 5-(hydroxyamino)pentylcarbamate		C₁₃H₂₀N₂O₃	详情	详情
(IV)	33390	4-[(5-[[(benzyloxy)carbonyl]amino]pentyl)(hydroxy)amino]-4-oxobutyric acid		C₁₇H₂₄N₂O₆	详情	详情
(V)	33391	benzyl 5-(3,6-dioxo-1,2-oxazinan-2-yl)pentylcarbamate		C₁₇H₂₂N₂O₅	详情	详情
(VI)	33392	benzyl 5-(hydroxy[4-[(5-nitropentyl)amino]-4-oxobutanoyl]amino)pentylcarbamate		C₂₂H₃₄N₄O₇	详情	详情
(VII)	33393	benzyl 5-[[4-([5-[acetyl(hydroxy)amino]pentyl]amino)-4-oxobutanoyl](hydroxy)amino]pentylcarbamate		C₂₄H₃₈N₄O₇	详情	详情

合成路线3

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).

参考文献中间体

【1】 Prelog, V.; Walser, A.; 75. Stoffweschselprodukte con actinomyceten. Uber die synthese der ferrioxamine B und D1. Helv Chim Acta 1962, 45, 631-637.
【2】 Bickel, H.; et al.; 153. Stoffweschselprodukte von mikroorganismen. Zur henntnis von desferrioxamin B. Helv Chim Acta 1963, 46, 1385-89.
【3】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Hopkins, S.J.; Liposome-Entrapped Desferrioxamine deferoxamine. Drugs Fut 1979, 4, 7, 500.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	33389	benzyl 5-(hydroxyamino)pentylcarbamate		C₁₃H₂₀N₂O₃	详情	详情
(V)	33391	benzyl 5-(3,6-dioxo-1,2-oxazinan-2-yl)pentylcarbamate		C₁₇H₂₂N₂O₅	详情	详情
(VII)	33393	benzyl 5-[[4-([5-[acetyl(hydroxy)amino]pentyl]amino)-4-oxobutanoyl](hydroxy)amino]pentylcarbamate		C₂₄H₃₈N₄O₇	详情	详情
(X)	33396	benzyl 5-[acetyl(hydroxy)amino]pentylcarbamate	92700-68-0	C₁₅H₂₂N₂O₄	详情	详情
(XI)	33397	N-(5-aminopentyl)-N-hydroxyacetamide		C₇H₁₆N₂O₂	详情	详情

合成路线4

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.

参考文献中间体

【1】 Bickel, H.; et al.; 153. Stoffweschselprodukte von mikroorganismen. Zur henntnis von desferrioxamin B. Helv Chim Acta 1963, 46, 1385-89.
【2】 Prelog, V.; Walser, A.; 75. Stoffweschselprodukte con actinomyceten. Uber die synthese der ferrioxamine B und D1. Helv Chim Acta 1962, 45, 631-637.
【3】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Hopkins, S.J.; Liposome-Entrapped Desferrioxamine deferoxamine. Drugs Fut 1979, 4, 7, 500.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(V)	33391	benzyl 5-(3,6-dioxo-1,2-oxazinan-2-yl)pentylcarbamate	C₁₇H₂₂N₂O₅	详情	详情
(VII)	33393	benzyl 5-[[4-([5-[acetyl(hydroxy)amino]pentyl]amino)-4-oxobutanoyl](hydroxy)amino]pentylcarbamate	C₂₄H₃₈N₄O₇	详情	详情
(VIII)	33394	N(1)-[5-[acetyl(hydroxy)amino]pentyl]-N(4)-(5-aminopentyl)-N(4)-hydroxysuccinamide	C₁₆H₃₂N₄O₅	详情	详情
(IX)	33395	benzyl 6,17,28-trihydroxy-7,10,18,21,29-pentaoxo-6,11,17,22,28-pentaazatriacont-1-ylcarbamate	C₃₃H₅₄N₆O₁₀	详情	详情

Extended Information