114870-03-0 Usage
Uses
1. Used in Pharmaceutical Industry:
Fondaparinux sodium is used as an antithrombotic agent for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism following major orthopedic surgery. It works by inhibiting thrombin generation without antithrombin action, making it a safer alternative to low molecular weight heparin (LMWH) and heparin.
2. Used in Medical Research:
Fondaparinux sodium has been used to test its neutralizing effect towards enterovirus D68-947 infection, showcasing its potential application in the field of virology and infectious diseases.
3. Used in Analytical Chemistry:
Fondaparinux sodium may be used in ultraviolet photodissociation (UVPD) measurements, indicating its potential application in the analysis and characterization of various chemical and biological samples.
Originator
Sanofi-Synthelabo (France)
Biochem/physiol Actions
Fondaparinux sodium is an antithrombotic anticoagulant, a Factor Xa inhibitor. Fondaparinux sodium is chemically related to low molecular weight heparins. Its pentasaccharide structure corresponds to the antithrombin III (ATIII) binding site of heparin. Fondaparinux sodium binding at this site potentiates the natural inhibitory effect of ATIII against factor Xa by a factor of approximately 300, which results in inhibition of thrombin generation.
Clinical Use
Prophylaxis of deep vein thrombosis
Treatment of deep vein thrombosis, pulmonary
embolism, unstable angina and after a myocardial
infarction
Synthesis
Starting from Dglucose,
D-cellobiose, and D-glucosamine, the production
process for the synthesis of the pentasaccharide involves
about 55 steps. The synthesis was accomplished by
preparing a fully-protected pentasaccharide, and then
converting it into the final product. The choice of protecting
groups was dictated by two factors: the need to introduce
sulfate substituents (O- as well as N-linked), carboxylate
groups and hydroxyl groups, in the proper positions on the
target molecule, and the constraints of current methods for
oligosaccharide synthesis, particularly the use of 2-azido
glucose derivatives to achieve stereoselective introduction of
α-D-linked glucosamine units. All the monosaccharide
synthons were obtained from glucose or from glucosamine, and the synthesis is outlined in the scheme.
Trisaccharide 108 and disaccharide 109 are the two key
building blocks in the synthesis. Coupling 108 and 109 was
carried out at -20°C in DCE. Fully protected pentasaccharide
110 was then converted into the target compound 10 using
traditional methods: saponification, O-sulfation, cleavage of
benzyl ethers with simultaneous reduction of azido into amino functions and finally N-sulfation. Preparation of
trisaccharide building block 108 started from 1,6-anhydrocellobiose
(111). Selective protection at 4’,6’ position was
achieved through benzylidenation to provide crude 112
which was converted into epoxide 113 by treatment with
sodium methoxide and benzylation. Compound 113 was isolated after filtration on silica gel and crystallization (m.p.
184-5°C). Trans-diaxial opening of the epoxide yielded the
2-azido derivative (66%) which was acetylated to give 114
(99%). The benzylidene was cleaved (92%) and the diol was
then converted into 115 by successive tritylation,
levulinoylation, detritylation, oxidation, methylation and hydrazinolysis (60% over the 6 steps). Imidate 116 was
prepared in the usual way from its hydroxyl precursor and
coupled with 115 to give O-linked trisaccharide 117 in 78%
yield. Compound 117 was acetolysed (91%), the anomeric
acetate was cleaved by benzylamine in ether (100%) and
imidate 108 was obtained by reaction with potassium
carbonate and trichloroacetonitrile at room temperature (α,
β- mixture with α as the predominant isomer, 76%). The
preparation of the other building block 109 is described as
following. Selective 6-acetylation of 118 by N -
acetylimidazole in DCE gave 119 in 60% yield. Treatment
of 119 with 120 using DCE/pyridinium perchlorate and
followed dechloroacetylation using hydrazinedithiocarbonate
afforded the crystalline disaccharide 109.
Drug interactions
Potentially hazardous interactions with other drugs
Increased risk of bleeding in combination with any
other drugs that affect coagulation.
Metabolism
Although not fully evaluated, there is no evidence of
fondaparinux metabolism and in particular no evidence
for the formation of active metabolites.
Fondaparinux is excreted to 64-77% by the kidney as
unchanged compound.
Check Digit Verification of cas no
The CAS Registry Mumber 114870-03-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,4,8,7 and 0 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 114870-03:
(8*1)+(7*1)+(6*4)+(5*8)+(4*7)+(3*0)+(2*0)+(1*3)=110
110 % 10 = 0
So 114870-03-0 is a valid CAS Registry Number.
114870-03-0Relevant articles and documents
Synthesis of methyl glycoside derivatives of tri- and penta-saccharides related to the antithrombin III-binding sequence of heparin, employing cellobiose as a key starting-material.
Ichikawa,Monden,Kuzuhara
, p. 37 - 64 (2007/10/02)
Two key synthons for the title pentasaccharide derivative, methyl O-(methyl 2-O-benzoyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)-6-O-acetyl- 2-azido - 3-O- benzyl-2-deoxy-beta-D-glucopyranoside and O-(methyl 2,3-di-O-benzyl-4-O- chloroacetyl-beta-D-glucopyranosyluronate)-(1----4)-3,6-di-O-acetyl-2-az ido-2- deoxy-alpha-D- glucopyranosyl bromide, were prepared from a common starting material, cellobiose. They were coupled to give a tetrasaccharide derivative that underwent O-dechloroacetylation to the corresponding glycosyl acceptor. Its condensation with the known 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide afforded a 77% yield of suitably protected pentasaccharide, methyl O-(6-O- acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)- O- (methyl 2,3- di-O-benzyl-beta-D-glucopyranosyluronate)-(1----4)-O-(3,6-di-O-acetyl-2- azido-2 - deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2-O-benzoyl-3-O-benzyl-alpha-L- idopyranosyluronate)- (1----4)-6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranoside. Sequential deprotection and sulfation gave the decasodium salt of methyl O-(2- deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-(1----4)-O-(be ta-D- glucopyranosyl-uronic acid)-(1----4)-O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-alpha-D-gluco pyranosyl)- (1----4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1----4)-2-deoxy-2- sulfamido-6-O- sulfo-beta-D-glucopyranoside (3). In a similar way, the trisaccharide derivative, the hexasodium salt of methyl O-(2-deoxy-2-sulfamido-6-O-sulfo-alpha-D- glucopyranosyl)- (1----4)-O-(beta-D-glucopyranosyluronic acid)-(1----4)-2-deoxy-2-sulfamido-3,6- di-O- sulfo-alpha-D-glucopyranoside (4) was synthesized from methyl O-(6-O-acetyl-2- azido- 3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2,3-di-O- benzyl-beta- D-glucopyranosyluronate)-3,6-di-O-acetyl-2-azido-2-deoxy-alpha-D- glucopyranoside. The pentasaccharide 3 binds strongly to antithrombin III with an association constant almost equivalent to that of high-affinity heparin, but the trisaccharide 4 appears not to bind.
