70-51-9 Usage
Description
Deferoxamine was introduced in the 1960s for chelation of
iron. It is synthesized by removing a central iron molecule
from ferrioxamine B, a compound obtained from the
microorganism Streptomyces pilosus. Deferoxamine binds to
iron from ferritin and forms ferrioxamine, a very stable and
water-soluble chelate with a characteristic reddish color.
Originator
Deferoxamine,Novartis,Germany
Uses
Different sources of media describe the Uses of 70-51-9 differently. You can refer to the following data:
1. Chelating agent (iron).
2. Deferoxamine is used for the treatment of both acute iron
intoxication and chronic iron overload due to transfusiondependent
anemias. It has also been used in trials for malaria
treatment and for aluminum chelation in hemodialysis
patients. Studies of a rat model of intracerebral hemorrhage
have noted that deferoxamine treatment reduced oxidative
stress from iron release, indicating a possible role in preventing
damage associated with hemorrhagic strokes.
Manufacturing Process
O-Benzylhydroxylamine hydrochloride (4.7 g, 29.7 mmol) was mixed with 5
ml of water and 11 ml of methanol at 0°C and the pH adjusted to 4.7 using 6
N KOH. The aldehyde, 4-cyanobutanal (2.6 mL, 27 mmol) was added to the
hydroxylamine and the mixture allowed to warm to room temperature. The pH
was maintained by addition of further 6 N KOH. After 1 h, the reaction was
cooled to 0°C, and sodium cyanoborohydride (1.26 g, 20 mmol) was added.
The pH was adjusted to 3 and maintained by addition of saturated HCl in
methanol. When the pH stabilized, the reaction was warmed to room temperature and stirred for 3 h at a PH of 3. The reaction mixture was then
poured into ether and made basic with 6 N KOH. The aqueous layer was
extracted with ether (3x50 mL). The extracts were combined, washed with
brine, and dried over magnesium sulfate. The solvents were removed and the
resulting liquid distilled at 150°-151°C (0.6 mm) to give 4.65 g (84% of Obenzyl-N-(4-cyanobutyl)hydroxylamine. 2.8 g (13.7 mmol) of the above
prepared hydroxylamine in 23 ml of pyridine and 2.1 g (20.8 mmol) of
succcinic anhydride, initially heated at 100°C for 1.5 h then allowed to cool to
room temperature and stirred overnight. The pyridine was removed in vacuum
and the residue was dissolved in a minimal amount of chloroform, and the
residue was dissolved in ether, which was extracted three times with 20%
potassium bicarbonate (3x50 mL). The aqueous solutions were combined,
acidified, extracted with ether, dried, filtered and evaporated; the residue was
then chromotagraphed on silica gel to give 4.12 g (98%) of N-(4-cyanobutylN-(benzyloxy)succinamic acid.2.6 g (12.75 mmol) of O-benzyl-N-(4-cyanobutyl)hydroxylamine, 17.24 mL of
pyridine and 17.2 mL of acetic anhydride were stirred under argon at room
temperature for 24 h. Then the excess pyridine and acetic acid anhydride
were removed by vacuum. The resulting oil was taken up in chloroform, which
was extracted with 1 N HCl (2x50mL), washed with sodium bicarbonate and
brine, dried, over sodium sulfate, filtered and evaporated to give 3.4 g
(100%) of N-(4-cyanobutyl)-N-(benzyloxy)acetamide as a light oil. 1.4 g (5.7
mmol) of this product, 2.6 g Raney nickel, 15 ml of ammonia saturated
methanol and 4 ml of saturated ammonium hydroxide were cooled in a ice
bath and anhydrous ammonia was allowed to bubble through the solution for
10 min. The bottle was pressurized to 50 psi with hydrogen and shook for 3 h.
Then the catalyst was filtered and the solvents evaporated. The crude material
was chromatografed on silica gel to gave a 1.25 g (88%) of N-(5-
aminopentyl)-N-(benzyloxy)acetamide.1 g (4 mmol), of the above acetamide, 1.46 g (4.79 mmol) of N-(4-
cyanobutyl-N-(benzyloxy)succinamic acid, 1.24 g (6 mmol) of DCC and 70 mg
of DMAP was cooled to 0°C for 0.55 h in 28 mL of chloroform. The mixture
was allowed to warm to room temperature and stirred 24 h. Then it was again
cooled to 0°C, filtered and chromatografed to yield 2.1 g (98%) of N-(4-
cyanobutyl)-3-[{5-N-benzyloxy)acetamido)pentyl}carbomoyl]-Obenzylpropionohydroxamic acid. This product (1 g) was hydrogeneted by
analogue with N-(4-cyanobutyl)-N-(benzyloxy)acetamide using Nickel Raney
as catalyst to give 1 g (88%) N-(5-aminopentyl)-3-[{5-(N -
benzyloxyacetamido)pentyl}carbomoyl]-O-benzylpropionohydroxamic acid,
which produced by the reaction with DCC described above 0.78 g (88%) of N-
[5-[3-[{4-cyanobutyl)(benzyloxy)-carbomoyl]propionaminoamido]pentyl}-3-
[{5-(N-bebzyloxyacetamido)pentyl]-carbomoyl]-O-benzylpropionohydroxamic
acid. The purity of all products confirmed with1H-NMR and elemental
analyses. The last compound (0.165 g, 0.2 mmol) was reduced in methanol,
2.7 mL of 0.1 N HCl and 0.27 g of 10% Pd on C. The hydrogenation was
carried out at one atmosphere of hydrogene for 7.5 hrs. The solution was
filtered, the solvents were removed and the residue was washed with cold
methanol, and then chloroform to give 0.1 g (84%) of product. This material
had melting point 167°-168°C [Prelog, supra] and was identical to an
authentic sample by 300 MHz NMR [sample of deferrioxamine B supplied by
dr. Heirich H. Peter at Ciba-Geigy, Basel, Switzerland].
Environmental Fate
Localized infusion or injection site reactions may occur
with deferoxamine administration, such as pain, urticaria
and flushing of the skin. Hypersensitivity reactions have
been documented with both acute and chronic administration
of deferoxamine. Some of the more serious side effects
include infusion rate-related hypotension, renal insufficiency,
neurotoxicity, growth retardation, pulmonary
toxicity, and infections. Deferoxamine may induce venous
dilation when given at doses greater than 15 mg kg-1 h-1
leading to poor venous return, depressed cardiac output,
and eventually hypotension. Increased levels of histamine
have been noted during hypotensive episodes, although
pretreatment with antihistamines has not been shown to
stop the reaction. An acute decrease in glomerular filtration
rate and renal plasma flow secondary to hypotension is the
possible mechanism underlying the nephrotoxicity induced
by deferoxamine. Depletion of iron, translocation of copper,
and chelation of other trace elements including zinc may
interfere with critical iron-dependent enzymes, causing
oxidative damage within various tissues. These are possible
mechanisms thought to be responsible for deferoxamineinduced
neurotoxicity, growth retardation, and pulmonary
toxicity. In vitro studies have shown that deferoxamine
inhibits the synthesis of prostaglandin, hemoglobin, ferritin,
collagen, and DNA. The iron–deferoxamine complex, ferrioxamine,
is a growth factor for many bacteria and fungi.
Deferoxamine has been associated with Yersinia enterocolitica
overgrowth and fatal cases of mucormycosis with prolonged
therapy.
Check Digit Verification of cas no
The CAS Registry Mumber 70-51-9 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 0 respectively; the second part has 2 digits, 5 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 70-51:
(4*7)+(3*0)+(2*5)+(1*1)=39
39 % 10 = 9
So 70-51-9 is a valid CAS Registry Number.
InChI:InChI=1/C25H48N6O8/c1-21(32)29(37)18-9-3-6-16-27-22(33)12-14-25(36)31(39)20-10-4-7-17-28-23(34)11-13-24(35)30(38)19-8-2-5-15-26/h37-39H,2-20,26H2,1H3,(H,27,33)(H,28,34)
70-51-9Relevant articles and documents
Convergent Synthesis of Macrocyclic and Linear Desferrioxamines
Chiu, Cheng-Hsin,Chung, Wen-Sheng,Jheng, Ting-Cian,Mong, Kwok-Kong Tony,Peng, Bo-Chun
, (2020/06/17)
Polyhydroxamate desferrioxamines (DFO) are nontoxic siderophores endowed with high potential for development of therapeutic chelating agents. Herein, we report a modular and convergent strategy for diverse synthesis of macrocyclic and linear DFOs. The strategy employed orthogonally protected N-hydroxy-N-succinylcadaverine building blocks, which allowed bidirectional extension of the DFO structure. The efficiency of the new strategy was demonstrated by the total synthesis of 44-membered macrocyclic DFO-T1, as well as four related DFO compounds in 11–13 linear steps and 2.1 %–10 % overall yields. Comparison of the iron binding affinity of the DFOs revealed DFO-E as the best chelator.
Glycation Cross-link Breakers to Increase Resistance to Enzymatic Degradation
-
, (2013/12/03)
The present invention relates to a method to treat a grafts, implant, scaffold, and constructs, including allografts, xenografts, autografts, and prosthetics comprising collagen, with an inhibitor of collagen cross-links and/or advanced glycation endproducts (AGE), in order to alleviate the mechanical weakness induced by the cross-links The invention also provides for kits for use in the operating theater during autograft, allograft or xenograft procedures, or for preparing allograft, xenografts or prosthetics that have not been already treated prior to packaging. The kit comprises a first agent or agents that inhibit collagen cross-links and/or advanced glycation endproducts, instructions for use, optionally a wash or rinse agent, and a device for containing the graft and first agent.
Imaging of Enzyme Activity
-
, (2008/06/13)
This invention relates to biochemistry and magnetic resonance imaging.
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